pantetheine has been researched along with pantethine* in 147 studies
8 review(s) available for pantetheine and pantethine
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Natural Molecules and Neuroprotection: Kynurenic Acid, Pantethine and α-Lipoic Acid.
The incidence of neurodegenerative diseases has increased greatly worldwide due to the rise in life expectancy. In spite of notable development in the understanding of these disorders, there has been limited success in the development of neuroprotective agents that can slow the progression of the disease and prevent neuronal death. Some natural products and molecules are very promising neuroprotective agents because of their structural diversity and wide variety of biological activities. In addition to their neuroprotective effect, they are known for their antioxidant, anti-inflammatory and antiapoptotic effects and often serve as a starting point for drug discovery. In this review, the following natural molecules are discussed: firstly, kynurenic acid, the main neuroprotective agent formed via the kynurenine pathway of tryptophan metabolism, as it is known mainly for its role in glutamate excitotoxicity, secondly, the dietary supplement pantethine, that is many sided, well tolerated and safe, and the third molecule, α-lipoic acid is a universal antioxidant. As a conclusion, because of their beneficial properties, these molecules are potential candidates for neuroprotective therapies suitable in managing neurodegenerative diseases. Topics: Animals; Antioxidants; Humans; Kynurenic Acid; Metabolic Networks and Pathways; Neurodegenerative Diseases; Neuroprotection; Neuroprotective Agents; Oxidative Stress; Pantetheine; Thioctic Acid | 2021 |
OLD AND NEW NEUROENDOCRINE MOLECULES: SOMATOSTATIN, CYSTEAMINE, PANTETHINE AND KYNURENINE.
The aim of this review is to commemorate Hans Selye, endocrinologist, the most famous researchers of stress and to briefly summarize the major features of somatostatin (SST), cysteamine (CysA) and patethine (PAN) in neuroendocrinological aspect, which are closely related to his scientific work. In addition, some metabolites of kynurenine pathway (KP) were also mentioned in this paper, as new, possible target molecules in neuroendocrinology. R. Guillemin and A. V. Schally were the main pioneers of the discovery of SST in the 1970's. SST primarily is known as an inhibitor of growth hormone secretion and additionally reduces the gastric acid and pepsin release and also the gastroduodenal mucosal blood flow. These effects are very important in the pathophysiology of peptic ulcer bleeding, which is related to the CysA-evoked perforating duodenal ulcer experimental stress model in rats developed by Selye and Szabo. CysA is a naturally occurring duodenal ulcerogen, which depletes SST in the gastric mucosa and certain brain regions. Furthermore, in addition to depleting SST, CysA also causes adrenocortical necrosis, suggesting an interaction between the central/peripheral nervous system and the neuroendocrine system. The antioxidant PAN, formulated besides the CysA, has similar effects: it attenuates the levels of SST and prolactin in the cerebral cortex and hypothalamus through the accumulation of CysA within cells throughout the body. As new perspectives the KP may be involved in the modulation of neuroendrocrine processes: different agonists and antagonists of glutamate receptors regulate the hypothalamic-pituitary-adrenal axis and kynurenic acid augments the anxiolytic stress responses in neonatal chicks. The pro-inflammatory cytokine-induced and the toxic heavy oil contaminations-evoked alterations in the KP indirectly contribute to the development of neuroendocrine disorders. In summary, there have been highly important developments in neuroendocrinology since the early findings of Selye. Although there are as yet relatively few data about the potential role of kynurenines in neuroendocrinology, the results already achieved are extremely noteworthy and immensely promising. Topics: Animals; Cysteamine; History, 20th Century; Humans; Kynurenine; Neuroendocrinology; Neurosecretory Systems; Pantetheine; Rats; Signal Transduction; Somatostatin; Tryptophan | 2014 |
Pantethine. Monograph.
Topics: Animals; Antioxidants; Apolipoproteins B; Cataract; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Hyperlipidemias; Lipid Peroxides; Pantetheine | 2010 |
Current medical aspects of pantethine.
Pantethine, the stable disulfide form of pantetheine, is the major precursor of coenzyme A, which plays a central role in the metabolism of lipids and carbohydrates. Coenzyme A is a cofactor in over 70 enzymatic pathways, including fatty acid oxidation, carbohydrate metabolism, pyruvate degradation, amino acid catabolism, haem synthesis, acetylcholine synthesis, phase II detoxification, acetylation, etc. Pantethine has beneficial effects in vascular disease, it able to decrease the hyperlipidaemia, moderate the platelet function and prevent the lipid-peroxidation. Moreover its neuro-endocrinological regulating role, its good influence on cataract and cystinosis are also proved. This molecule is a well-tolerated therapeutic agent; the frequency of its side-effect is very low and mild. Based on these preclinical and clinical data, it could be recommended using this compound as adjuvant therapy. Topics: Acetylcholine; Animals; Antioxidants; Atherosclerosis; Blood Platelets; Cataract; Central Nervous System; Coenzyme A; Cystine; Cystinosis; Dietary Carbohydrates; Fatty Acids; Humans; Hyperlipidemias; Hypolipidemic Agents; Lipid Peroxidation; Oxidation-Reduction; Pantetheine; Pantothenic Acid; Pyruvates | 2009 |
Dietary and nutraceutical options for managing the hypertriglyceridemic patient.
Scientific evidence continues to accumulate regarding fasting serum triglycerides as an independent risk factor for coronary heart disease. In response, the National Cholesterol Education Program has revised the acceptable level of fasting triglycerides from <200 mg/dL to <150 mg/dL. A significant percentage of Americans suffer from hypertriglyceridemia, and considering the expanding numbers of individuals who are physically inactive, overweight, and suffering from the metabolic syndrome, it is expected that these numbers will continue to rise over the next decade. Fortunately, nutraceutical and lifestyle options have been shown to substantially and consistently reduce this risk factor. This review will focus on management options for the hypertriglyceridemic patient with an emphasis on nicotinic acid, pantethine, fish oils (eicosapentaenoic and docosahexaenoic acids), and modified carbohydrate diets. Topics: Dietary Carbohydrates; Energy Intake; Evidence-Based Medicine; Exercise; Fasting; Fish Oils; Humans; Hypertriglyceridemia; Metabolic Syndrome; Niacin; Obesity; Pantetheine; Practice Guidelines as Topic; Risk Factors; Risk Reduction Behavior; Severity of Illness Index; Triglycerides; Weight Loss | 2006 |
Can drugs or micronutrients prevent cataract?
Cataract is the major cause of blindness and of visual impairment worldwide, so its prevention is of the greatest importance. At present no drug therapy is licensed for use in the UK or the US, so the only treatment for cataract is by surgery, which is expensive and has adverse effects. This article reviews research on prevention of cataract by a variety of agents, including micronutrients as well as drugs. Benefits have been claimed for many compounds or mixtures and this review concentrates on those most extensively studied. Information on possible benefits of putative anticataract agents comes from a variety of approaches, from laboratory experiments, both in vitro and in vivo, to epidemiological studies in patients. Sorbitol-lowering drugs were the first to be examined systematically and progressed to clinical trials which were disappointing, and now the entire rationale for their use in prevention of cataract is questionable. Micronutrients showed little promise in animals but came to clinical trial in patients with cataract without the publication of any major benefit. Pantethine showed more promise in animal studies but the only clinical trial was abandoned early. A variety of laboratory and epidemiological evidence supports the benefits of aspirin-like drugs but there has been no trial specifically in patients with cataract. Add-on studies to trials of aspirin for other indications have not been encouraging. Research into other compounds is interesting but less advanced. Topics: Aldehyde Reductase; Aspirin; Cataract; Clinical Trials as Topic; Drug Design; Estrogens; Glutathione; Humans; Pantetheine | 2001 |
Preclinical and clinical studies with cysteamine and pantethine related to the central nervous system.
1. Cysteamine is formed by degradation of coenzyme A (CoA) and causes somatostatin (SS), prolactin and noradrenaline depletion in the brain and peripheral tissues. 2. Cysteamine influences several behavioral processes, like active and passive avoidance behavior, open-field activity, kindled seizures, pain perception and SS-induced barrel rotation. 3. Cysteamine has several established (cystinosis, radioprotection, acetaminophen poisoning) and theoretical (Huntington's disease, prolactin-secreting adenomas) indications in clinical practice. 4. Pantethine is a naturally occurring compound which is metabolized to cysteamine. 5. Pantethine depletes SS, prolactin and noradrenaline with lower efficacy compared to that of cysteamine. 6. Pantethine is well tolerated by patients and has been suggested to treatment of atherosclerosis. The other possible clinical indications (alcoholism, Parkinson's disease, instead of cysteamine) are discussed. Topics: Alcoholism; Animals; Central Nervous System; Central Nervous System Diseases; Cerebrovascular Disorders; Cysteamine; Humans; Pantetheine; Parkinson Disease | 1990 |
[Atherosclerosis and prostaglandins: new biochemical frontiers of a more rational therapy].
Topics: Arteriosclerosis; Cholesterol; Diet; Epoprostenol; Female; Humans; Lipoproteins; Male; Pantetheine; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Risk; Thromboxanes; Triglycerides | 1987 |
12 trial(s) available for pantetheine and pantethine
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Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study.
This study aimed to explore the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration (PKAN).. A single-arm, open-label study was conducted. All subjects received pantethine during the 24-week period of treatment. The primary endpoints were change of the Unified Parkinson's Disease Rating Scale (UPDRS) I-III and Fahn-Marsden (FM) score from baseline to week 24 after treatment.. Fifteen children with PKAN were enrolled, and all patients completed the study. After 24 weeks of treatment with pantethine at 60 mg/kg per day, there was no difference in either UPDRS I-III (t = 0.516, P = 0.614) or FM score (t = 0.353, P = 0.729) between the baseline and W24. Whereas the rates of increase in UPDRS I-III (Z = 2.614, p = 0.009) and FM scores (Z = 2.643, p = 0.008) were slowed. Four patients (26.7%) were evaluated as "slightly improved" by doctors through blinded video assessment. Patients with lower baseline UPDRS I-III or FM scores were more likely to be improved. The quality of life of family members improved after pantethine treatment, evaluated by PedsQL TM 2.0 FIM scores, whereas the quality of life of the patients was unchanged at W24, evaluated by PedsQL TM 4.0 and PedsQL TM 3.0 NMM. Serum level of CoA was comparable between baseline and W24. There was no drug related adverse event during the study.. Pantethine could not significantly improve motor function in children with PKAN after 24 weeks treatment, but it may delay the progression of motor dysfunction in our study. Pantethine was well-tolerated at 60 mg/kg per day.. Clinical trial registration number at www.chictr.org.cn :ChiCTR1900021076, Registered 27 January2019, the first participant was enrolled 30 September 2018, and other 14 participants were enrolled after the trial was registered. Topics: Child; Female; Humans; Male; Pantetheine; Pantothenate Kinase-Associated Neurodegeneration; Pilot Projects; Quality of Life; Treatment Outcome | 2020 |
Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation.
High serum concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD) risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP) guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to 16) or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040) and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively), and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively) that reached significance by week 16 (P=0.042). An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027) and 16 (P=0.010). The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants eligible for statins according to NCEP guidelines. Topics: Adult; Anticholesteremic Agents; Biomarkers; Cholesterol; Cholesterol, LDL; Combined Modality Therapy; Coronary Disease; Female; Florida; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Middle Aged; Ontario; Pantetheine; Patient Selection; Practice Guidelines as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome | 2014 |
Pantethine, a derivative of vitamin B(5) used as a nutritional supplement, favorably alters low-density lipoprotein cholesterol metabolism in low- to moderate-cardiovascular risk North American subjects: a triple-blinded placebo and diet-controlled invest
Safety and efficacy of a biologically active derivative of vitamin B(5) (pantethine) on total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) metabolism was studied in North American subjects at conventional low to moderate cardiovascular disease (CVD) risk. A total of 120 subjects initiated a therapeutic lifestyle change (TLC) diet 4 weeks before randomization (baseline) and maintained the diet throughout a 16-week study period; at baseline, subjects were randomized in a triple-blinded manner to either pantethine (600 mg/d, baseline to week 8, and 900 mg/d, weeks 9-16) or identically labeled, nonbiologically active placebo (n = 60 per group). We hypothesized that pantethine would lower TC and low-density lipoprotein in low-CVD-risk North American subjects in a similar manner as reported in high-CVD-risk subjects studied mainly in Italy and Japan. While sustaining a TLC diet and in comparison with placebo, pantethine demonstrated significant (P < .005) and sustained reductions (from baseline to week 16) in TC (6 mg/dL, 0.16 mmol/L, 3%), LDL-C (4 mg/dL, 0.10 mmol/L, 4%), and apolipoprotein B (4 mg/dL, 0.04 g/L, 5%). Our data suggest that pantethine supplementation for 16 weeks (600 mg/d for weeks 1-8 then 900 mg/d for weeks 9-16) is safe and significantly lowers TC and LDL-C over and above the effect of TLC diet alone. Although the absolute magnitude of these effects was small in these low- to moderate-risk North Americans (4-6 mg/dL), the results are noteworthy as prior studies have shown that, for each 1 mg/dL (0.026 mmol/L) reduction in LDL-C, there is a concomitant 1% reduction in overall future CVD risk. Topics: Adult; Apolipoproteins B; Cardiovascular Diseases; Cholesterol; Cholesterol, LDL; Diet; Dietary Supplements; Double-Blind Method; Female; Health Promotion; Humans; Life Style; Male; Middle Aged; North America; Pantetheine; Risk; Vitamin B Complex | 2011 |
Comparison of the effects of pantethine and fursultiamine on plasma gastrointestinal peptide levels in healthy volunteers.
Pantethine and fursultiamine have been evaluated for their clinical usefulness in the treatment and prevention of uncomplicated postoperative adhesive intestinal obstruction. In recent years, the actions of drugs used to treat gastrointestinal diseases have been elucidated pharmacologically from the viewpoints of gastrointestinal peptide levels. We examined the effects of pantethine and fursultiamine on plasma levels of calcitonin gene-related peptide (CGRP)-, vasoactive intestinal polypeptide (VIP)-, motilin- and substance P (SP)-like immunoreactive substances (IS) in healthy subjects. An open-labeled study was conducted on five healthy volunteers. Each subject was administered a single oral dose of pantethine, fursultiamine and placebo at intervals of one month. Venous blood samples were collected before and at 20, 40, 60, 90, 120, 180 and 240 min after each administration. Plasma peptide levels were measured using a highly sensitive enzyme immunoassay. A single oral dose of pantethine resulted in significant increases of plasma CGRP- and VIP-IS levels compared to placebo. Furthermore, areas under the plasma concentration-time curves (AUC(0-240)) of CGRP- and VIP-IS were significantly higher after pantethine administration compared with placebo. On the other hand, fursultiamine had no effect on plasma levels and AUC(0-240) of CGRP-, VIP-, motilin- and SP-IS. This study demonstrated the different effects of pantethine and fursultiamine from the viewpoint of plasma gastrointestinal peptide changes. The pharmacological effects of pantethine may be closely related to the changes in plasma CGRP- and VIP-IS levels. Topics: Adult; Calcitonin Gene-Related Peptide; Drug Administration Schedule; Drug Evaluation, Preclinical; Fursultiamin; Gastrointestinal Tract; Humans; Male; Molecular Targeted Therapy; Motilin; Pantetheine; Substance P; Vasoactive Intestinal Peptide; Vitamin B Complex | 2011 |
The effects of pantethine on fatty liver and fat distribution.
Although the prognosis of fatty liver depends on its causes, we feel from our clinical experience that fatty liver with hypertriglyceridemia has a good prognosis and responds well to treatment. In this study, 600 mg/day of pantethine was administered to 16 outpatients with fatty liver and hypertriglyceridemia for six months or longer to examine whether the drug improved fatty liver using abdominal plain computed tomography (CT). Nine of the 16-pantethine patients were no longer diagnosed as having fatty liver after the study period. An chi2 test indicated the significant disappearance of fatty liver. At the same time, the visceral fat calculated from the CT image passing the umbilical region was also significantly reduced. On the contrary, the subcutaneous fat area tended to increase, so the ratio of the visceral-to-subcutaneous fat area was reduced significantly. This indicates triglycerides may be pooled in the body as hepato-visceral fat and subcutaneous fat, and that pantethine may transfer fat from the liver and viscera to the subcutaneous tissue. This suggests that visceral fat deposition and fatty liver occurring with hypertriglyceridemia may have a common basis, probably excessive matrixes, and that pantethine may simultaneously improve the two conditions. Topics: Abdomen; Aged; Case-Control Studies; Fatty Liver; Female; Humans; Liver; Male; Middle Aged; Pantetheine; Tomography, X-Ray Computed | 2000 |
Physiological and performance responses to supplementation with thiamin and pantothenic acid derivatives.
The purpose of this study was to investigate the physiological and performance responses to supplementation with allithiamin and pantethine. On two separate occasions, six highly trained cyclists [maximum O2 consumption or VO2max 61.8 (2.1) ml x kg(-1) x min(-1)] performed a 50-km steady-state ride on a cycle ergometer at a workload corresponding to approximately 60% of VO2max followed by a 2000-m time trial. For 7 days prior to each ride, subjects daily ingested either a placebo (PL) or a combination of 1 g of allithiamin and 1.8 g of a 55%/45% pantethine/pantothenic acid compound (AP). Treatments were administered using a randomized, double-blind, counter-balanced design. During the 50km ride, measures of heart rate, respiratory gas exchange and ratings of perceived exertion were recorded at 5, 15, 25, 35 and 45 km. Blood samples were collected at 10, 20, 30, 40 and 50 km and analyzed for lactate, glucose and free fatty acids. Blood samples for the analysis of lactate were also collected 3 and 5 min after the completion of the 2000-m time trial. There were no significant differences in any of the measured parameters between experimental conditions. Time to complete the 2000-m time trial was also not significantly different between experimental conditions [PL 178.2 (8.4), AP 170.7 (10.2) s; P=0.58]. These results suggest that, despite the reported enhanced absorption properties, supplementation with allithiamin and pantethine does not alter exercise metabolism or exercise performance. Topics: Adult; Bicycling; Blood Glucose; Double-Blind Method; Exercise; Exercise Test; Fatty Acids, Nonesterified; Heart Rate; Humans; Lactic Acid; Male; Oxygen Consumption; Pantetheine; Pantothenic Acid; Pulmonary Gas Exchange; Thiamine | 1998 |
[A double-blind clinical trial--the effects of pantethine on serum lipids in patients with hyperlipidemia].
Topics: Adult; Aged; Cholesterol; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Hyperlipidemias; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1989 |
Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.
In a single-blind, crossover, completely randomized study, the effects of oral treatment with pantethine or placebo on fatty acid composition of plasma and platelet phospholipids were investigated in 10 IIa hyperlipoproteinemic patients. A significant decrease of total cholesterol and total phospholipids was observed both in plasma and in platelets after a twenty-eight-day treatment. In plasma, pantethine induced a decrease of the ratio sphingomyelin/phosphatidylcholine. Moreover, a relative increase of n3-polyunsaturated fatty acids both in plasma and in platelet phospholipids and a decrease of arachidonic acid in plasma phospholipids were observed. These results indicate that pantethine can affect plasma and platelet lipid composition with possibly favorable influences on the determinants of cell membrane fluidity. Topics: Administration, Oral; Adult; Aged; Blood Platelets; Clinical Trials as Topic; Double-Blind Method; Fatty Acids; Female; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Pantetheine; Phosphatidylcholines; Phospholipids; Sphingomyelins; Sulfhydryl Compounds | 1987 |
[Effects of pantethine on blood lipids].
Topics: Adult; Aged; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Coronary Disease; Female; Humans; Lipids; Male; Middle Aged; Pantetheine; Risk; Sulfhydryl Compounds; Triglycerides | 1986 |
Pantethine versus fenofibrate in the treatment of type II hyperlipoproteinemia.
Topics: Clinical Trials as Topic; Double-Blind Method; Female; Fenofibrate; Humans; Hyperlipoproteinemia Type II; Lipids; Lipoproteins; Male; Pantetheine; Propionates; Random Allocation; Sulfhydryl Compounds | 1985 |
Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia.
Pantethine (P), the stable disulphate form of pantetheine, major component and precursor of coenzyme A, was evaluated within a double-blind protocol (8 weeks for P or for a corresponding placebo) in 29 patients, 11 with type IIB hyperlipoproteinemia, 15 with type IV, and 3 with an isolated reduction of high density lipoprotein cholesterol (HDL-C) levels. In type IIB patients, P (300 mg t.i.d.) determined a highly significant lowering of plasma total and low density lipoprotein (LDL) associated cholesterol (-13.5% for both parameters). In the same patients, HDL-C levels increased about 10% at the end of treatment. Switching from P to placebo was associated with a rapid return to the baseline cholesterolemia. Both in type IIB and type IV patients, plasma triglyceride levels were reduced around 30%, when P was given as the first treatment; when it was preceded by placebo, reductions were less striking (respectively, -17.8% for type IIB and -13.0% for type IV, at the end of P treatment). HDL-C levels were not increased by P, either in type IV, and in the patients with low HDL cholesterolemia. In type IV, LDL cholesterol levels showed a variable response to P: they tended to increase when below 132 mg/dl, prior to treatment, and to be reduced when above this level. This study provides evidence for a significant hypocholesterolemic effect of P, a natural compound free of overt side effects. It also indicates that P may raise HDL-C levels in type IIB patients, while moderately reducing triglyceridemia. Topics: Adult; Cholesterol; Cholesterol, HDL; Clinical Trials as Topic; Female; Humans; Hyperlipoproteinemias; Hypolipidemic Agents; Lipoproteins; Lipoproteins, HDL; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1984 |
[Clinical study of the lipotropic activity of the preparation Fosfolip].
A randomized and double blind experiment has been made over 50 patients and 25 checks, by giving a dosage of 3 Fosfolip (calcium salt of phosphorylcholine chlorid with pantethine) capsules a day. The analysis results has been reported in the work. In none case the product had secondary no desired effects; while therapeutical possibilities have been resulted in hepatosis, dyslipidosis and as energetic tonic in atherosclerotic subjects. Topics: Adult; Aged; Arteriosclerosis; Choline; Clinical Trials as Topic; Double-Blind Method; Drug Combinations; Female; Humans; Hyperlipidemias; Lipids; Liver Diseases; Male; Middle Aged; Pantetheine; Phosphorylcholine; Sulfhydryl Compounds | 1983 |
127 other study(ies) available for pantetheine and pantethine
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Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression.
Colon adenocarcinoma (COAD) is one of the most prevalent malignancies, with poor prognosis and lack of effective treatment targets. Squalene synthase (FDFT1) is an upstream enzyme of squalene epoxidase (SQLE) in cholesterol biosynthesis. In a previous study, we revealed that SQLE promotes colon cancer cell proliferation in vitro and in vivo. Here, we investigate the prognostic value of FDFT1 in stage I-III COAD and explore the potential underlying mechanisms. Squalene synthase was significantly upregulated in stage I-III COAD and positively correlated with poor differentiation and advanced tumor stage. High expression of FDFT1 was an independent predictor of overall and relapse-free survival, and the nomograms based on FDFT1 could effectively identify patients at high risk of poor outcome. Squalene synthase accelerated colon cancer cell proliferation and promoted tumor growth. Lack of FDFT1 resulted in accumulating NAT8 and D-pantethine to lower reactive oxygen species levels and inhibit colon cancer cell proliferation. Moreover, the combined inhibition of FDFT1 and SQLE induced a greater suppressive effect on cell proliferation and tumor growth than single inhibition. Taken together, these results indicate that FDFT1 predicts poor prognosis in stage I-III COAD and has the tumor-promoting effect on COAD through regulating NAT8 and D-pantethine. Targeting both FDFT1 and SQLE is a more promising therapy than their single inhibition for stage I-III COAD. Topics: Acetyltransferases; Aged; Aged, 80 and over; Animals; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Farnesyl-Diphosphate Farnesyltransferase; Female; Humans; Male; Mice; Middle Aged; Neoplasm Staging; Pantetheine; Prognosis; Reactive Oxygen Species; Squalene Monooxygenase; Xenograft Model Antitumor Assays | 2022 |
Long-Term Pantethine Treatment Counteracts Pathologic Gene Dysregulation and Decreases Alzheimer's Disease Pathogenesis in a Transgenic Mouse Model.
The low-molecular weight thiol pantethine, known as a hypolipidemic and hypocholesterolemic agent, is the major precursor of co-enzyme A. We have previously shown that pantethine treatment reduces amyloid-β (Aβ)-induced IL-1β release and alleviates pathological metabolic changes in primary astrocyte cultures. These properties of pantethine prompted us to investigate its potential benefits in vivo in the 5XFAD (Tg) mouse model of Alzheimer's disease (AD).1.5-month-old Tg and wild-type (WT) male mice were submitted to intraperitoneal administration of pantethine or saline control solution for 5.5 months. The effects of such treatments were investigated by performing behavioral tests and evaluating astrogliosis, microgliosis, Αβ deposition, and whole genome expression arrays, using RNAs extracted from the mice hippocampi. We observed that long-term pantethine treatment significantly reduced glial reactivity and Αβ deposition, and abrogated behavioral alteration in Tg mice. Moreover, the transcriptomic profiles revealed that after pantethine treatment, the expression of genes differentially expressed in Tg mice, and in particular those known to be related to AD, were significantly alleviated. Most of the genes overexpressed in Tg compared to WT were involved in inflammation, complement activation, and phagocytosis and were found repressed upon pantethine treatment. In contrast, pantethine restored the expression of a significant number of genes involved in the regulation of Αβ processing and synaptic activities, which were downregulated in Tg mice. Altogether, our data support a beneficial role for long-term pantethine treatment in preserving CNS crucial functions altered by Aβ pathogenesis in Tg mice and highlight the potential efficiency of pantethine to alleviate AD pathology. Topics: Aggression; Alzheimer Disease; Amyloid beta-Peptides; Animals; Disease Models, Animal; Drug Administration Schedule; Hippocampus; Humans; Male; Mice; Mice, Transgenic; Pantetheine; Phagocytosis; Time Factors | 2019 |
Efficient one-pot enzymatic synthesis of dephospho coenzyme A.
Dephospho coenzyme A (depCoA) is the last intermediate for CoA biosynthesis, and it can be used as a transcription initiator to prepare CoA-linked RNA by in vitro transcription. However, commercially available depCoA is expensive. We hereby describe a simple and efficient enzymatic synthesis of depCoA in a single-step from commercially available and inexpensive oxidized pantethine (Ox-Pan) and ATP. A plasmid (pCoaDAa) was constructed to co-express and co-purify two enzymes pantothenate kinase (PanK/coaA) and phosphopantetheine adenylyltransferase (PPAT/coaD). Starting from Ox-Pan and ATP, two different synthetic routes of one-pot reaction catalyzed by PanK and PPAT, followed by a simple column purification step, afforded depCoA and its oxidized dimer (Ox-depCoA) with high yields and purity. The simplicity and low cost of our method should make depCoA easily accessible to a broad scientific community, and promote research on CoA-related areas in biology and biomedicine. Topics: Adenosine Triphosphate; Amino Acid Sequence; Base Sequence; Chemistry Techniques, Synthetic; Cloning, Molecular; Coenzyme A; Escherichia coli; Nucleotidyltransferases; Oxidation-Reduction; Pantetheine; Phosphotransferases (Alcohol Group Acceptor); Plasmids | 2018 |
Mutations in PPCS, Encoding Phosphopantothenoylcysteine Synthetase, Cause Autosomal-Recessive Dilated Cardiomyopathy.
Coenzyme A (CoA) is an essential metabolic cofactor used by around 4% of cellular enzymes. Its role is to carry and transfer acetyl and acyl groups to other molecules. Cells can synthesize CoA de novo from vitamin B5 (pantothenate) through five consecutive enzymatic steps. Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second step of the pathway during which phosphopantothenate reacts with ATP and cysteine to form phosphopantothenoylcysteine. Inborn errors of CoA biosynthesis have been implicated in neurodegeneration with brain iron accumulation (NBIA), a group of rare neurological disorders characterized by accumulation of iron in the basal ganglia and progressive neurodegeneration. Exome sequencing in five individuals from two unrelated families presenting with dilated cardiomyopathy revealed biallelic mutations in PPCS, linking CoA synthesis with a cardiac phenotype. Studies in yeast and fruit flies confirmed the pathogenicity of identified mutations. Biochemical analysis revealed a decrease in CoA levels in fibroblasts of all affected individuals. CoA biosynthesis can occur with pantethine as a source independent from PPCS, suggesting pantethine as targeted treatment for the affected individuals still alive. Topics: Amino Acid Sequence; Animals; Biosynthetic Pathways; Cardiomyopathy, Dilated; Carnitine; Child, Preschool; Coenzyme A; Demography; Drosophila; Enzyme Stability; Female; Fibroblasts; Genes, Recessive; Heart; High-Throughput Nucleotide Sequencing; Homozygote; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Mutation; Pantetheine; Pedigree; Peptide Synthases; Reproducibility of Results; Saccharomyces cerevisiae | 2018 |
Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma-bearing mice under doxorubicin treatment is not connected with their ROS scavenging potential.
To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice.. Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears. Changes in ROS content in B16 melanoma cells under Dx, SeMet, and D-Pt action in vitro were measured by incubation with fluorescent dyes dihydrodichlorofluoresceindiacetate (DCFDA, H2O2-specific) and dihydroethidium (DHE, O2--specific), and further analysis at FL1 (DCFDA) or FL2 channels (DHE) of FACScan flow cytometer. The impact of aforementioned compounds on functional status of mitochondria was measured by Rhodamine 123 assay and further analysis at FL1 channel of FACScan flow cytometer.. Selenomethionine (1200 µg/kg) and D-pantethine (500 mg/kg) in combination with Dx (10 mg/kg) significantly reduced tumor-induced neutrophilia, lymphocytopenia, and leukocytosis in comparison to Dx treatment alone. Moreover, SeMet and D-Pt decreased several side effects of Dx, namely an elevated creatinine level in blood and monocytosis, thus normalizing health conditions of B16 melanoma-bearing animals.. Our results showed that antioxidants selenomethionine and D-pantethine possess significant nephroprotective and myeloprotective activity toward Dx action on murine B16 melanoma in vivo, but fail to boost a survival of B16 melanoma-bearing animals. The observed cytoprotective effects of studied antioxidants are not directly connected with their ROS scavenging. Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Dose-Response Relationship, Drug; Doxorubicin; Melanoma, Experimental; Mice; Mice, Inbred C57BL; Pantetheine; Reactive Oxygen Species; Selenomethionine | 2017 |
Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer's disease: Alleviation by pantethine.
Astrocytes play critical roles in central nervous system homeostasis and support of neuronal function. A better knowledge of their response may both help understand the pathophysiology of Alzheimer's disease (AD) and implement new therapeutic strategies. We used the 5xFAD transgenic mouse model of AD (Tg thereafter) to generate astrocyte cultures and investigate the impact of the genotype on metabolic changes and astrocytes activation. Metabolomic analysis showed that Tg astrocytes exhibited changes in the glycolytic pathway and tricarboxylic acid (TCA) cycle, compared to wild type (WT) cells. Tg astrocytes displayed also a prominent basal inflammatory status, with accentuated reactivity and increased expression of the inflammatory cytokine interleukin-1 beta (IL-1β). Compensatory mechanisms were activated in Tg astrocytes, including: i) the hexose monophosphate shunt with the consequent production of reducing species; ii) the induction of hypoxia inducible factor-1 alpha (HIF-1α), known to protect against amyloid-β (Aβ) toxicity. Such events were associated with the expression by Tg astrocytes of human isoforms of both amyloid precursor protein (APP) and presenilin-1 (PS1). Similar metabolic and inflammatory changes were induced in WT astrocytes by exogenous Aβ peptide. Pantethine, the vitamin B5 precursor, known to be neuroprotective and anti-inflammatory, alleviated the pathological pattern in Tg astrocytes as well as WT astrocytes treated with Aß. In conclusion, our data enlighten the dual pathogenic/protective role of astrocytes in AD pathology and the potential protective role of pantethine. Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Astrocytes; Cell Survival; Cells, Cultured; Citric Acid Cycle; Disease Models, Animal; Gene Expression; Glycolysis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Interleukin-1beta; Metabolomics; Mice; Mice, Transgenic; Pantetheine; Pentose Phosphate Pathway; Presenilin-1; RNA, Messenger | 2017 |
Pantethine Down-Regulates Leukocyte Recruitment and Inflammatory Parameters in a Mouse Model of Allergic Airway Inflammation.
BACKGROUND Migration of leukocytes into airways is the hallmark of allergic asthma. The aim of this study was to target the pathological process using pantethine, a pleiotropic natural compound which has been recently shown to down-regulate chemokine-driven T cell migration. MATERIAL AND METHODS Mice were sensitized to the Leishmania LACK antigen, then treated or not treated with pantethine and exposed to LACK or saline aerosol. After sacrifice of the animals, cells in the bronchoalveolar lavage were analyzed and inflammatory parameters were determined to evaluate inflammation seriousness. RESULTS As compared to untreated animals, pantethine-treated animals displayed a moderated response to the allergen, as documented by decreased infiltration of inflammatory cells (all types), in addition to reduced levels of lung Th2 cytokines and circulating LACK-specific IgE. CONCLUSIONS These data reveal the potential therapeutic importance of pantethine to moderate allergic asthma pathology. The compound has been previously shown to exert a broad range of protective activity in animals and in humans, with few or no adverse effects. Topics: Allergens; Animals; Antigens, Protozoan; Bronchoalveolar Lavage; Cytokines; Disease Models, Animal; Down-Regulation; Female; Inflammation; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Pantetheine; Protozoan Proteins | 2017 |
Antioxidants selenomethionine and D-pantethine decrease the negative side effects of doxorubicin in NL/Ly lymphoma-bearing mice.
To investigate the potential tissue-protective effects of antioxidants selenomethionine and D-pantethine applied together with doxorubicin (Dx) on NK/Ly lymphoma-bearing mice. The impact of this chemotherapy scheme on animal survival, blood cell profile, hepatotoxicity, glutathione level, and activity of glutathione-converting enzymes in the liver was compared with the action of Dx applied alone... The hematological profile of animals was studied by the analysis of blood smears under light microscopy. Hepatotoxicity of studied drugs was evaluated measuring the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, De Ritis ratio, and coenzyme A fractions by McDougal assay. Glutathione level in animal tissues was measured with Ellman reagent, and the activity of glutathione reductase, transferase, and peroxidase was measured using standard biochemical assays.. D-pantethine (500 mg/kg) and, to a lower extent, selenomethionine (600 µg/kg) partially reduced the negative side effects (leukocytopenia and erythropenia) of Dx (5 mg/kg) in NK/Ly lymphoma bearing animals on the 14th day of their treatment. This increased animal survival time from 47-48 to 60+ days and improved the quality of their life. This ability of D-pantethine and selenomethionine was realized via hepatoprotective and immunomodulating activities. D-pantethine also restored the levels of acid-soluble and free CoA in the liver of tumor-bearing animals, while selenomethionine caused the recovery of glutathione peroxidase levels in the liver, which was significantly diminished under Dx treatment. Both compounds decreased glutathione level in the liver, which was considerably induced by Dx.. Antioxidants selenomethionine and D-pantethine partially reversed the negative side effects of Dx in NK/Ly lymphoma-bearing mice and significantly increased the therapeutic efficiency of this drug in tumor treatment. Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Antioxidants; Aspartate Aminotransferases; Doxorubicin; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Liver; Lymphoma; Male; Mice; Mice, Inbred BALB C; Pantetheine; Selenomethionine; Tumor Cells, Cultured | 2016 |
Targeting microparticle biogenesis: a novel approach to the circumvention of cancer multidrug resistance.
Microparticles (MPs) are released from most eukaryotic cells after the vesiculation of the plasma membrane and serve as vectors of long and short-range signaling. MPs derived from multidrug resistant (MDR) cancer cells carry molecular components of the donor cell such as nucleic acids and proteins, and can alter the activity of drug-sensitive recipient cells through the transfer of their cargo. Given the substantial role of MPs in the acquisition and dissemination of MDR, we propose that the inhibition of MP release provides a novel therapeutic approach. This study characterises the effect of a panel of molecules known to act on MP-biosynthetic pathways. We demonstrate a differential effect by these molecules on MP inhibition that appear dependent on the release of intracellular calcium stores following activation with the calcium ionophore A23187. Calpain inhibitor, PD-150606; a selective inhibitor of Rho-associated, coiled-coil containing protein kinase (ROCK), Y-27632; and the vitamin B5 derivative pantethine, inhibited MP release only upon prior activation with A23187. Calpain inhibitor II showed significant inhibition in the absence of cell activation, whereas the vitamin B5 derivatives cystamine dihydrochloride and cysteamine hydrochloride showed no effect on MP inhibition under either condition. In contrast the classical pharmacological inhibitor of MDR, the calcium channel blocker Verapamil, showed an increase in MP formation on resting cells. These results suggest a potential role for calcium in the mechanism of action for PD-150606, Y-27632 and pantethine. These molecules, together with calpain inhibitor II have shown promise as modulators of MP release and warrant consideration as potential candidates for the development of an alternative therapeutic strategy for the prevention of MP-mediated MDR in cancer. Topics: Acrylates; Amides; Antineoplastic Agents; Breast Neoplasms; Calcimycin; Cell Line, Tumor; Cell-Derived Microparticles; Cystamine; Cysteamine; Drug Resistance, Neoplasm; Female; Humans; Molecular Targeted Therapy; Oligopeptides; Pantetheine; Pyridines; Verapamil | 2015 |
Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down-Regulation of CXCL12-Induced T Cell Migration.
Pantethine, a natural low-molecular-weight thiol, shows a broad activity in a large range of essential cellular pathways. It has been long known as a hypolipidemic and hypocholesterolemic agent. We have recently shown that it exerts a neuroprotective action in mouse models of cerebral malaria and Parkinson's disease through multiple mechanisms. In the present study, we looked at its effects on membrane lipid rafts that serve as platforms for molecules engaged in cell activity, therefore providing a target against inappropriate cell response leading to a chronic inflammation. We found that pantethine-treated cells showed a significant change in raft fatty acid composition and cholesterol content, with ultimate downregulation of cell adhesion, CXCL12-driven chemotaxis, and transendothelial migration of various T cell types, including human Jurkat cell line and circulating effector T cells. The mechanisms involved include the alteration of the following: (i) CXCL12 binding to its target cells; (ii) membrane dynamics of CXCR4 and CXCR7, the two CXCL12 receptors; and (iii) cell redox status, a crucial determinant in the regulation of the chemokine system. In addition, we considered the linker for activation of T cells molecule to show that pantethine effects were associated with the displacement from the rafts of the acylated signaling molecules which had their palmitoylation level reduced.. In conclusion, the results presented here, together with previously published findings, indicate that due to its pleiotropic action, pantethine can downregulate the multifaceted process leading to pathogenic T cell activation and migration. Topics: Animals; Cell Movement; Chemokine CXCL12; Cholesterol; Down-Regulation; Humans; Jurkat Cells; Lipids; Lymphocyte Activation; Pantetheine; Rats; Signal Transduction; T-Lymphocytes | 2015 |
Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding.
Endothelial cell (EC) damage in systemic sclerosis (SSc) is reflected by the shedding of microparticles (MPs). The aim of this study was to show that inhibiting MP release using pantethine or by inactivating ATP-binding cassette transporter A1 (ABCA1) ameliorates murine SSc.. First, the effects of pantethine on MP shedding and on basal oxidative and nitrosative stresses in ECs and fibroblasts were determined in vitro. The effects of pantethine were then tested in vivo. SSc was induced in BALB/c mice by daily intradermal injection of HOCl. Mice were simultaneously treated daily with pantethine by oral gavage.. In vitro, pantethine inhibited MP shedding from tumor necrosis factor-stimulated ECs and abrogated MP-induced oxidative and nitrosative stresses in ECs and fibroblasts. Ex vivo, pantethine also restored redox homeostasis in fibroblasts from mice with SSc. In vivo, mice with SSc displayed skin and lung fibrosis associated with increased levels of circulating MPs and markers of oxidative and endothelial stress, which were normalized by administration of pantethine or inactivation of ABCA1.. Pantethine is a well-tolerated molecule that represents a potential treatment of human SSc. Topics: Administration, Oral; Animals; ATP Binding Cassette Transporter 1; Bleomycin; Cell-Derived Microparticles; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Female; Fibroblasts; Homeostasis; Hypochlorous Acid; In Vitro Techniques; Injections, Intradermal; Mice; Mice, Inbred BALB C; Mice, Knockout; Oxidative Stress; Pantetheine; Scleroderma, Systemic; Treatment Outcome | 2015 |
Pantethine treatment is effective in recovering the disease phenotype induced by ketogenic diet in a pantothenate kinase-associated neurodegeneration mouse model.
Pantothenate kinase-associated neurodegeneration, caused by mutations in the PANK2 gene, is an autosomal recessive disorder characterized by dystonia, dysarthria, rigidity, pigmentary retinal degeneration and brain iron accumulation. PANK2 encodes the mitochondrial enzyme pantothenate kinase type 2, responsible for the phosphorylation of pantothenate or vitamin B5 in the biosynthesis of co-enzyme A. A Pank2 knockout (Pank2(-/-)) mouse model did not recapitulate the human disease but showed azoospermia and mitochondrial dysfunctions. We challenged this mouse model with a low glucose and high lipid content diet (ketogenic diet) to stimulate lipid use by mitochondrial beta-oxidation. In the presence of a shortage of co-enzyme A, this diet could evoke a general impairment of bioenergetic metabolism. Only Pank2(-/-) mice fed with a ketogenic diet developed a pantothenate kinase-associated neurodegeneration-like syndrome characterized by severe motor dysfunction, neurodegeneration and severely altered mitochondria in the central and peripheral nervous systems. These mice also showed structural alteration of muscle morphology, which was comparable with that observed in a patient with pantothenate kinase-associated neurodegeneration. We here demonstrate that pantethine administration can prevent the onset of the neuromuscular phenotype in mice suggesting the possibility of experimental treatment in patients with pantothenate kinase-associated neurodegeneration. Topics: Animals; Behavior, Animal; Brain; Cholesterol; Diet, Ketogenic; Energy Metabolism; Female; Heredodegenerative Disorders, Nervous System; Immunohistochemistry; Male; Membrane Potential, Mitochondrial; Mice; Mice, Knockout; Microscopy, Electron; Mitochondria; Motor Skills; Neurons; Pantetheine; Peripheral Nervous System; Phenotype; Phosphotransferases (Alcohol Group Acceptor); Sciatic Nerve; Triglycerides | 2014 |
The synthesis of minds and molecules leads to potential therapy for pantothenate kinase-associated neurodegeneration.
Topics: Animals; Diet, Ketogenic; Female; Heredodegenerative Disorders, Nervous System; Male; Pantetheine; Phosphotransferases (Alcohol Group Acceptor) | 2014 |
Development and validation of a stability-indicating LC-UV method for the determination of pantethine and its degradation product based on a forced degradation study.
Pantethine (d-bis-(N-pantothenyl-β-aminoethyl)-disulfide, PAN), the stable disulfide form of pantetheine, has beneficial effects in vascular diseases being able to decrease the hyperlipidaemia, moderate the platelet function and prevent the lipid peroxidation. Furthermore, recent studies suggested that PAN may be an effective therapeutic agent for cerebral malaria and, possibly, for neurodegenerative processes. Interestingly, in the literature, there were no data dealing with the chemical stability and the analytical aspects of PAN. Hence, in the present work the chemical stability of PAN was for the first time established through a forced degradation study followed by liquid chromatography tandem mass spectrometry investigation showing the formation of three degradation products of PAN (PD1, PD2 and POx) arising from hydrolytic, thermal and oxidative stresses. Based on these data a stability-indicating LC-UV method for simultaneous estimation of PAN, and its most relevant degradation product (PD1) was developed and validated; moreover the method allowed also the separation and the quantification of the preservative system, constituted by a paraben mixture. The method showed linearity for PAN (0.4-1.2mgmL(-1)), MHB, PHB (0.4-1.2μgmL(-1)) and PD1 (2.5-100μgmL(-1)); the precision, determined in terms of intra-day and inter-day precision, expressed as RSDs, were in the ranges 0.4-1.2 and 0.7-1.4, respectively. The method demonstrated to be accurate and robust; indeed the average recoveries were 100.2, 99.9, and 100.0% for PAN, MHB and PHB, respectively, and 99.9% for PD1. By applying small variations of the mobile phase composition, counter-ion concentration and pH the separation of analytes was not affected. Finally, the applicability of this method was evaluated analyzing the available commercial forms at release as well as during stability studies. Topics: Capsules; Chromatography, Liquid; Drug Stability; Limit of Detection; Molecular Structure; Pantetheine; Parabens; Tandem Mass Spectrometry; Ultraviolet Rays | 2014 |
Specific antioxidant compounds differentially modulate cytotoxic activity of doxorubicin and cisplatin: in vitro and in vivo study.
To use the antioxidant compounds (sodium selenite, selenomethionine, D-pantethine) for modulation of cytotoxic effect of doxorubicin and cisplatin toward wild type and drug-resistant mutants of several human tumor cells. Similar treatments were applied in vivo toward adult male Wistar rats.. Human tumor cells of different lines (HCT-116, Jurkat and HL-60) with various mechanisms of drug-resistance were treated with doxorubicin or cisplatin, alone or in combination with sodium selenite, selenomethionine, or D-pantethine. Cell viability, induction of apoptosis, and production of O2- radicals were measured. Activity of redox potential modulating enzymes was measured in the liver and blood plasma of adult male Wistar rats subjected to similar treatments.. All antioxidants used in physiologically harmless concentration inhibited cytotoxic action of doxorubicin toward tumor cells sensitive to chemotherapy treatment by 15%-30%, and slightly enhanced cytotoxic effect of this medicine toward drug-resistant malignant cells. At the same time, there was no significant effect of these antioxidants on cisplatin action. Such effects were accompanied by a complete inhibition of production of superoxide radicals induced by doxorubicin. The results of in vivo study in adult male Wistar rats were in agreement with the results of in vitro study of human tumor cells.. Protective effect of specific antioxidant agents during cytotoxic action of doxorubicin was demonstrated in vitro in drug-sensitive human tumor cells and in adult male Wistar rats, while there was no protective effect in drug-resistant sub-lines of these tumor cells during action of doxorubicin and cisplatin. Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Cisplatin; Doxorubicin; Drug Synergism; HCT116 Cells; HL-60 Cells; Humans; Jurkat Cells; Male; Oxidation-Reduction; Oxidoreductases; Pantetheine; Rats; Rats, Wistar; Selenomethionine; Sodium Selenite; Tumor Cells, Cultured | 2014 |
[Deceleration of cataract development in rats under the action of N-acetylcarnosine and D-pantethine mixture].
The effect of a mixture of N-acetylcarnosine and D-pantethine (1 : 1, m/m) on UV-A induced cataract in rats was studied. It is shown that instillation of a 5% mixture into the eyes or intraperitoneal injections (25 or 150 mg/kg) inhibit the formation of cataracts, starting from 82nd day of the experiment (p < 0.03), after which the protective effect of the mixture significantly increases (p = 0.0003). UV-A irradiation significantly (p < 0.01) increased the content of water-insoluble proteins in the lens. The use of the mixture of N-Acetylcarnosine and D-pantethine prevented (p < 0.001) an increase in the content of water-insoluble proteins caused by UV-A irradiation. Gel permeation chromatography data showed that, in the control group, water insoluble proteins consist of 3 fractions (40 kDa, 100 - 200 kDa, and1000 kDa). UV-A irradiation reduced the amount of protein in fraction 1 and increases the amount of protein in the fractions 2 and 3. The use of the mixture of N-acetylcarnosine and D-pantethine reduced the effects of UV-A light. The authors attribute the effect of the N-acetylcarnosine and D-pantethine mixture to their chaperone-like properties. Topics: Animals; Carnosine; Cataract; Chromatography, Gel; Drug Combinations; Eye Proteins; Injections, Intraperitoneal; Lens, Crystalline; Male; Ophthalmic Solutions; Pantetheine; Protective Agents; Protein Aggregates; Radiation Injuries, Experimental; Rats; Rats, Wistar; Solubility; Ultraviolet Rays | 2014 |
Self-assembly of protein aggregates in ageing disorders: the lens and cataract model.
Cataract, neurodegenerative disease, macular degeneration and pathologies of ageing are often characterized by the slow progressive destabilization of proteins and their self-assembly to amyloid-like fibrils and aggregates. During normal cell differentiation, protein self-assembly is well established as a dynamic mechanism for cytoskeletal organization. With the increased emphasis on ageing disorders, there is renewed interest in small-molecule regulators of protein self-assembly. Synthetic peptides, mini-chaperones, aptamers, ATP and pantethine reportedly regulate self-assembly mechanisms involving small stress proteins, represented by human αB-crystallin, and their targets. Small molecules are being considered for direct application as molecular therapeutics to protect against amyloid and protein aggregation disorders in ageing cells and tissues in vivo. The identification of specific interactive peptide sites for effective regulation of protein self-assembly is underway using conventional and innovative technologies. The quantification of the functional interactions between small stress proteins and their targets in vivo remains a top research priority. The quantitative parameters controlling protein-protein interactions in vivo need characterization to understand the fundamental biology of self-assembling systems in normal cells and disorders of ageing. Topics: Aging; alpha-Crystallin B Chain; Animals; Cataract; Lens, Crystalline; Models, Biological; Molecular Chaperones; Pantetheine; Protein Conformation; Protein Unfolding | 2013 |
Metabolic perturbation of an essential pathway: evaluation of a glycine precursor of coenzyme A.
Pantetheine and its corresponding disulfide pantethine play a key role in metabolism as building blocks of coenzyme A (CoA), an essential cofactor utilized in ~4% of primary metabolism and central to fatty acid, polyketide, and nonribosomal peptide synthases. Using a combination of recombinant engineering and chemical synthesis, we show that the disulfide of N-pantoylglycyl-2-aminoethanethiol (GlyPan), with one fewer carbon than pantetheine, can rescue a mutant E. coli strain MG1655ΔpanC lacking a functional pantothenate synthetase. Using mass spectrometry, we show that the GlyPan variant is accepted by the downstream CoA biosynthetic machinery, ultimately being incorporated into essential acyl carrier proteins. These findings point to further flexibility in CoA-dependent pathways and offer the opportunity to incorporate orthogonal analogues. Topics: Acyl Carrier Protein; Amino Acid Sequence; Chromatography, High Pressure Liquid; Coenzyme A; Disulfides; Electrophoresis, Polyacrylamide Gel; Escherichia coli; Glycine; Mass Spectrometry; Metabolic Networks and Pathways; Molecular Sequence Data; Pantetheine; Peptide Synthases; Phosphotransferases (Alcohol Group Acceptor); Urea | 2013 |
D-pantethine has vitamin activity equivalent to d-pantothenic acids for recovering from a deficiency of D-pantothenic acid in rats.
D-Pantethine is a compound in which two molecules of D-pantetheine bind through an S-S linkage. D-Pantethine is available from commercial sources as well as from D-pantothenic acid. We investigated if D-pantethine has the same vitamin activity as D-pantothenic acid by comparing the recovery from a deficiency of D-pantothenic acid in rats. D-Pantothenic acid-deficient rats were developed by weaning rats on a diet lacking D-pantothenic acid for 47 d. At that time, the urinary excretion of D-pantothenic acid was almost zero, and the body weight extremely low, compared with the control (p<0.05); the contents of free D-pantothenic acid were also significantly reduced in comparison with those of controls (p<0.05). D-Pantothenic acid-deficient rats were administered a diet containing D-pantothenic acid or D-pantethine for 7 d. D-Pantethine and D-pantothenic acid contents of the diets were equimolar in forms of D-pantothenic acid. We compared various parameters concerning nutritional status between rats fed D-pantothenic acid- and D-pantethine-containing diets. The recoveries of body weight, tissue weights, and tissue concentrations of free D-pantothenic acid, dephospho-CoA, CoA, and acetyl-CoA were identical between rats fed diets containing D-pantothenic acid and D-pantethine. Thus, the biological efficiency for recovering from a deficiency of D-pantothenic acid in rats was equivalent between D-pantothenic acid and D-pantethine. Topics: Acetyl Coenzyme A; Animals; Body Weight; Coenzyme A; Diet; Male; Organ Size; Pantetheine; Pantothenic Acid; Rats; Rats, Wistar; Vitamins; Weaning | 2013 |
Integrated electroosmotic perfusion of tissue with online microfluidic analysis to track the metabolism of cystamine, pantethine, and coenzyme A.
We have developed an approach that integrates electroosmotic perfusion of tissue with a substrate-containing solution and online microfluidic analysis of products, in this case thiols. Using this approach we have tracked the metabolism of cystamine, pantethine and CoA in the extracellular space of organotypic hippocampal slice cultures (OHSCs). Currently, little is known about coenzyme A (CoA) biodegradation and even less is known about the regulation and kinetic characteristics for this sequential multienzyme reaction. We found that the steady state percentage yields of cysteamine from cystamine and pantethine during the transit through OHSCs were 91% ± 4% (SEM) and 0.01%-0.03%, respectively. The large difference in the yields of cysteamine can be used to explain the drugs' different toxicities and clinical effectiveness against cystinosis. The kinetic parameters of the enzyme reaction catalyzed by the ectoenzyme pantetheinase are KM,C/α = 4.4 ± 1.1 mM and Vmax,C = 29 ± 3 nM/s, where α is the percentage yield of pantethine to pantetheine through disulfide exchange. We estimate that the percentage yield of pantethine to pantetheine through disulfide exchange is approximately 0.5%. Based on the formation rate of cysteamine in the OHSCs, we obtained the overall apparent Michaelis constant and maximum reaction rate for sequential, extracellular CoA degradation in an in situ environment, which are K'M = 16 ± 4 μM, V'max = 7.1 ± 0.5 nM/s. Kinetic parameters obtained in situ, although difficult to measure, are better representations of the biochemical flux in the living organism than those from isolated enzymes in vitro. Topics: Calibration; Coenzyme A; Cystamine; Electroosmosis; Extracellular Space; Hippocampus; Microfluidic Analytical Techniques; Pantetheine; Perfusion; Systems Integration | 2013 |
The role of nutraceutical supplements in the treatment of dyslipidemia.
The combination of a lipid-lowering diet and scientifically proven nutraceutical supplements has the ability to significantly reduce low-density lipoprotein (LDL) cholesterol, increase LDL particle size, decrease LDL particle number, lower trigylcerides and very LDL levels, and increase total and high-density lipoprotein 2b cholesterol. In addition, inflammation, oxidative stress, and immune responses are decreased. In several prospective clinical trials, coronary heart disease and cardiovascular disease have been reduced with many nutraceutical supplements. This nutritional and nutraceutical supplement treatment is a valid alternative for patients who are intolerant to statins, cannot take other drugs for the treatment of dyslipidemia, or prefer alternative treatments. This new approach to lipid management to decrease vascular disease utilizes a functional medicine approach with a broader treatment program that will address the multitude of steps involved in lipid-induced vascular damage. Topics: Atherosclerosis; Dietary Fats; Dietary Supplements; Dyslipidemias; Humans; Lipoproteins; Lipoproteins, VLDL; Oxidative Stress; Pantetheine; Resveratrol; Stilbenes; Tocotrienols; Triglycerides; Vascular Diseases; Vasodilator Agents | 2012 |
Pantethine rescues phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase deficiency in Escherichia coli but not in Pseudomonas aeruginosa.
Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4'-phosphopantothenate to 4'-phosphopantetheine, was confirmed in Escherichia coli. Utilizing this regulated coaBC strain, it was further demonstrated that E. coli can effectively metabolize pantethine to bypass the requirement for coaBC. Interestingly, pantethine cannot be used by Pseudomonas aeruginosa to obviate coaBC. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by coaA in E. coli and coaX in P. aeruginosa. Topics: Biosynthetic Pathways; Carboxy-Lyases; Escherichia coli; Escherichia coli Proteins; Gene Deletion; Genes, Essential; Genetic Complementation Test; Multienzyme Complexes; Pantetheine; Peptide Synthases; Pseudomonas aeruginosa | 2011 |
Impaired Coenzyme A metabolism affects histone and tubulin acetylation in Drosophila and human cell models of pantothenate kinase associated neurodegeneration.
Pantothenate kinase-associated neurodegeneration (PKAN is a neurodegenerative disease with unresolved pathophysiology. Previously, we observed reduced Coenzyme A levels in a Drosophila model for PKAN. Coenzyme A is required for acetyl-Coenzyme A synthesis and acyl groups from the latter are transferred to lysine residues of proteins, in a reaction regulated by acetyltransferases. The tight balance between acetyltransferases and their antagonistic counterparts histone deacetylases is a well-known determining factor for the acetylation status of proteins. However, the influence of Coenzyme A levels on protein acetylation is unknown. Here we investigate whether decreased levels of the central metabolite Coenzyme A induce alterations in protein acetylation and whether this correlates with specific phenotypes of PKAN models. We show that in various organisms proper Coenzyme A metabolism is required for maintenance of histone- and tubulin acetylation, and decreased acetylation of these proteins is associated with an impaired DNA damage response, decreased locomotor function and decreased survival. Decreased protein acetylation and the concurrent phenotypes are partly rescued by pantethine and HDAC inhibitors, suggesting possible directions for future PKAN therapy development. Topics: Acetylation; Animals; Coenzyme A; Disease Models, Animal; Drosophila; Histones; Humans; Pantetheine; Pantothenate Kinase-Associated Neurodegeneration; Protein Processing, Post-Translational; Tubulin | 2011 |
Pantethine rescues a Drosophila model for pantothenate kinase-associated neurodegeneration.
Pantothenate kinase-associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. Topics: Animals; Brain; Coenzyme A; Drosophila; Gene Expression Regulation; Humans; Mitochondria; Models, Biological; Mutation; Oxidative Stress; Oxygen; Pantetheine; Pantothenate Kinase-Associated Neurodegeneration; Phenotype; Phosphotransferases (Alcohol Group Acceptor) | 2010 |
Enhancement of L-3-hydroxybutyryl-CoA dehydrogenase activity and circulating ketone body levels by pantethine. Relevance to dopaminergic injury.
The administration of the ketone bodies hydroxybutyrate and acetoacetate is known to exert a protective effect against metabolic disorders associated with cerebral pathologies. This suggests that the enhancement of their endogenous production might be a rational therapeutic approach. Ketone bodies are generated by fatty acid beta-oxidation, a process involving a mitochondrial oxido-reductase superfamily, with fatty acid-CoA thioesters as substrates. In this report, emphasis is on the penultimate step of the process, i.e. L-3-hydroxybutyryl-CoA dehydrogenase activity. We determined changes in enzyme activity and in circulating ketone body levels in the MPTP mouse model of Parkinson's disease. Since the active moiety of CoA is pantetheine, mice were treated with pantethine, its naturally-occurring form. Pantethine has the advantage of being known as an anti-inflammatory and hypolipidemic agent with very few side effects.. We found that dehydrogenase activity and circulating ketone body levels were drastically reduced by the neurotoxin MPTP, whereas treatment with pantethine overcame these adverse effects. Pantethine prevented dopaminergic neuron loss and motility disorders. In vivo and in vitro experiments showed that the protection was associated with enhancement of glutathione (GSH) production as well as restoration of respiratory chain complex I activity and mitochondrial ATP levels. Remarkably, pantethine treatment boosted the circulating ketone body levels in MPTP-intoxicated mice, but not in normal animals.. These finding demonstrate the feasibility of the enhancement of endogenous ketone body production and provide a promising therapeutic approach to Parkinson's disease as well as, conceivably, to other neurodegenerative disorders. Topics: Acyl Coenzyme A; Adenosine Triphosphate; Animals; Brain Diseases, Metabolic; Dopamine; Electron Transport Complex I; Encephalitis; Energy Metabolism; Glutathione; Hydroxybutyrate Dehydrogenase; Ketone Bodies; Male; Mice; Mice, Inbred C57BL; Nerve Degeneration; Neurons; Neuroprotective Agents; Oxidative Stress; Pantetheine; Parkinsonian Disorders; Substantia Nigra; Up-Regulation | 2010 |
Topical apolipoprotein A-1 may have a beneficial effect on the corneal epithelium in a mouse model of dry eye: a pilot study.
Dry-eye syndrome affects millions of individuals and it is essential to develop effective therapeutic agents for the treatment of this complex condition. The goal of this study was to evaluate the effect of apolipoprotein A (ApoA)-1 and its synergistic action with d-pantethine (DP) on corneal epithelial disorders in dry-eye mouse model.. Aqueous tear production of C57BL/6J Jms Slc male mice aged 10 to 12 weeks were inhibited by subcutaneous scopolamine injection and mice were placed in a continuous airflow blower to create desiccating environmental stress. During desiccation, 1 eye of each mouse was treated with ApoA-1 (0.01%, 0.04%, or 0.1%) or ApoA-1 (0.04%) + DP (0.05%, 0.1%, or 0.2%) and the other control eye was instilled with phosphate-buffered saline 4 times daily for 5 days. Phenol red thread test, corneal fluorescein staining (score, 0-4), and measurement of corneal epithelial thickness measurements were performed.. Significant reductions of staining scores and higher corneal epithelial thickness values were observed in both ApoA-1- and ApoA-1 + DP-treated groups compared with untreated dry-eye mouse and phosphate-buffered saline-treated group.. These results suggest that ApoA-1 and DP may be potential therapeutic agents for ocular surface epithelial disorders in patients with dry eye. Topics: Administration, Topical; Animals; Apolipoprotein A-I; Corneal Diseases; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Dry Eye Syndromes; Epithelium, Corneal; Male; Mice; Mice, Inbred C57BL; Ophthalmic Solutions; Pantetheine; Pilot Projects; Treatment Outcome | 2008 |
Protection against cerebral malaria by the low-molecular-weight thiol pantethine.
We report that administration of the low-molecular-weight thiol pantethine prevented the cerebral syndrome in Plasmodium berghei ANKA-infected mice. The protection was associated with an impairment of the host response to the infection, with in particular a decrease of circulating microparticles and preservation of the blood-brain barrier integrity. Parasite development was unaffected. Pantethine modulated one of the early steps of the inflammation-coagulation cascade, i.e., the transbilayer translocation of phosphatidylserine at the cell surface that we demonstrated on red blood cells and platelets. In this, pantethine mimicked the inactivation of the ATP-binding-cassette transporter A1 (ABCA1), which also prevents the cerebral syndrome in this malaria model. However, pantethine acts through a different pathway, because ABCA1 activity was unaffected by the treatment. The mechanisms of pantethine action were investigated, using the intact molecule and its constituents. The disulfide group (oxidized form) is necessary to lower the platelet response to activation by thrombin and collagen. Thio-sensitive mechanisms are also involved in the impairment of microparticle release by TNF-activated endothelial cells. In isolated cells, the effects were obtained by cystamine that lacks the pantothenic moiety of the molecule; however, the complete molecule is necessary to protect against cerebral malaria. Pantethine is well tolerated, and it has already been administered in other contexts to man with limited side effects. Therefore, trials of pantethine treatment in adjunctive therapy for severe malaria are warranted. Topics: Animals; Blood-Brain Barrier; Cell Line; Cell Line, Transformed; Female; Humans; Malaria, Cerebral; Mice; Mice, Inbred CBA; Molecular Weight; Pantetheine; Permeability; Plasmodium berghei; Platelet Aggregation; Platelet Aggregation Inhibitors; Syndrome | 2008 |
An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment.
Once the plant coenzyme A (CoA) biosynthetic pathway has been elucidated by comparative genomics, it is feasible to analyze the physiological relevance of CoA biosynthesis in plant life. To this end, we have identified and characterized Arabidopsis (Arabidopsis thaliana) T-DNA knockout mutants of two CoA biosynthetic genes, HAL3A and HAL3B. The HAL3A gene encodes a 4'-phosphopantothenoyl-cysteine decarboxilase that generates 4'-phosphopantetheine. A second gene, HAL3B, whose gene product is 86% identical to that of HAL3A, is present in the Arabidopsis genome. HAL3A appears to have a predominant role over HAL3B according to their respective mRNA expression levels. The hal3a-1, hal3a-2, and hal3b mutants were viable and showed a similar growth rate as that in wild-type plants; in contrast, a hal3a-1 hal3b double mutant was embryo lethal. Unexpectedly, seedlings that were null for HAL3A and heterozygous for HAL3B (aaBb genotype) displayed a sucrose (Suc)-dependent phenotype for seedling establishment, which is in common with mutants defective in beta-oxidation. This phenotype was genetically complemented in aaBB siblings of the progeny and chemically complemented by pantethine. In contrast, seedling establishment of Aabb plants was not Suc dependent, proving a predominant role of HAL3A over HAL3B at this stage. Total fatty acid and acyl-CoA measurements of 5-d-old aaBb seedlings in medium lacking Suc revealed stalled storage lipid catabolism and impaired CoA biosynthesis; in particular, acetyl-CoA levels were reduced by approximately 80%. Taken together, these results provide in vivo evidence for the function of HAL3A and HAL3B, and they point out the critical role of CoA biosynthesis during early postgerminative growth. Topics: Acyl Coenzyme A; Arabidopsis; Arabidopsis Proteins; Coenzyme A; DNA, Bacterial; Fatty Acids; Molecular Sequence Data; Mutagenesis, Insertional; Pantetheine; Phenotype; RNA, Messenger; Seedlings; Seeds; Sucrose | 2006 |
Inhibition of acetyl-CoA carboxylase by cystamine may mediate the hypotriglyceridemic activity of pantethine.
Pantethine is a versatile and well-tolerated hypolipidemic agent whose efficacy in this regard appears to be mediated by its catabolic product cystamine, a nucleophile which avidly attacks disulfide groups. An overview of pantethine research suggests that the hypotriglyceridemic activity of pantethine reflects cystamine-mediated inhibition of the hepatic acetyl-CoA carboxylase, which can be expected to activate hepatic fatty acid oxidation. Inhibition of HMG-CoA reductase as well as a more distal enzyme in the cholesterol synthetic pathway may account for pantethine's hypocholesterolemic effects. If pantethine does indeed effectively inhibit hepatic acetyl-CoA carboxylase, it may have adjuvant utility in the hepatothermic therapy of obesity. As a safe and effective compound of natural origin, pantethine merits broader use in the management of hyperlipidemias. Topics: Acetyl-CoA Carboxylase; Animals; Cholesterol; Cystamine; Fatty Acids; Humans; Hydroxymethylglutaryl CoA Reductases; Hypolipidemic Agents; Liver; Models, Biological; Obesity; Pantetheine; Triglycerides | 2001 |
The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.
Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse.. A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine.. Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters.. Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model. Topics: Animals; Cataract; Cysteamine; Disease Models, Animal; Disease Progression; Female; Lens, Crystalline; Male; Mice; Mice, Inbred Strains; Pantetheine; Ultraviolet Rays | 2000 |
Pantethine.
Topics: Humans; Pantetheine | 1998 |
Reduction of pantethine in rabbit ocular lens homogenate.
In several animal models, preliminary studies have indicated that pantethine may inhibit cataract formation. Therefore, preclinical trials need to be conducted to study the pharmacology of pantethine in the ocular lens and to establish its efficacy. Since pantethine, which is a disulfide, can undergo a variety of chemical modifications such as reduction and formation of mixed disulfides, a detailed study was first conducted to determine the stability of pantethine in rabbit lens homogenate. A knowledge of the stability of pantethine in lens homogenate was necessary to establish if pantethine could be metabolized in the time it takes to harvest and homogenize a lens. The results of this study will be used to establish a protocol for harvesting and homogenizing lens samples. Pantethine (100 microM) is completely reduced to pantetheine in rabbit lens homogenate in about 16 min. About 1.5% of the pantethine added to lens homogenate forms a mixed disulfide with lens proteins, and the remainder is found in the supernatant. The supernatant pantethine concentration decreases exponentially as a function of time, and the terminal half-life for this process is 3.3 min. The free supernatant pantetheine concentration increases in pseudo first order manner as a function of time with a rate constant of 4.3 min. Pantethinase activity is not significant, because the free supernatant pantetheine concentration did not decrease. The exact mechanism of pantethine reduction in rabbit lens homogenate remains to be determined. Topics: Animals; Cattle; Chromatography, High Pressure Liquid; Drug Stability; Electrochemistry; Lens, Crystalline; Oxidation-Reduction; Pantetheine; Rabbits | 1997 |
Loss of cytoskeletal proteins and lens cell opacification in the selenite cataract model.
This study of lens protein composition found that some cytoskeletal proteins were degraded during the earliest stages of cataract formation. Cataract was induced in 13-14 day old rats by a single subcutaneous injection of sodium selenite (19 mumol kg-1). By 24 hr after the injection of selenite, the ratio of insoluble to soluble protein increased as lens opacification began. The increase in insoluble protein aggregates was correlated with an accelerated loss of proteins having molecular weights of 42, 55/57 and 235 kDa which reacted with antibodies to the cytoskeletal proteins actin, tubulin/vimentin and spectrin, respectively. We observed the loss of 49, 60 and 90 kDa proteins which were not identified. In the lenses of animals protected from protein aggregation and opacification by administration of 1.5 mmol kg-1 pantethine, the pattern of proteins in SDS-PAGE gels resembled the pattern for proteins from transparent lenses of normal untreated animals and loss of cytoskeletal proteins was prevented. Topics: Actins; Animals; Blotting, Western; Cataract; Crystallins; Cytoskeletal Proteins; Disease Progression; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Pantetheine; Rats; Rats, Sprague-Dawley; Sodium Selenite; Spectrin; Tubulin; Vimentin | 1997 |
Effect of selected anti-cataract agents on opacification in the selenite cataract model.
A systematic study of the anti-cataract activity of 14 reagents was conducted using the selenite model. The reagents or their derivatives were identified from literature reports of their potential effectiveness against cataract formation. The effects of each reagent were measured on the phase separation temperature, Tc, of lens homogenate in vitro. Tc is a direct measure of molecular interactions leading to protein aggregation. The protective effect of a single subcutaneous injection of each reagent [at a dose of 1.5 mmol (kg body weight)-1] on lens opacification was evaluated in vivo using rats administered selenite [at a dose of 19 mumol (kg body weight)-1] to initiate cataract formation. The strongest effects on lens opacification in vivo were observed with reagents having the strongest effect on Tc, in vitro. The weakest effects in vivo were observed with the reagents having the weakest effect on Tc, in vitro. The results were suggestive of a relationship between the effect of a reagent on Tc and protection against cataract formation in vivo. Topics: Animals; Antioxidants; Cataract; Chelating Agents; Disulfides; Pantetheine; Phosphates; Rats; Rats, Sprague-Dawley; Sodium Selenite; Temperature; Tissue Extracts | 1996 |
Delay or inhibition of rat lens opacification using pantethine and WR-77913.
Pantethine and the amino phosphorothioate, WR-77913, protected lenses against increased light scattering and opacification during cataract formation in five animal models: (1) radiation, (2) selenite, (3) galactose, (4) streptozotocin and (5) Royal College of Surgeons. In the radiation or selenite models, each test reagent was administered 15 to 30 min prior to initiation of cataract by a single injection of Na2SeO3 or a single exposure to 15 Gy (gray) gamma radiation. In the galactose, streptozotocin and Royal College of Surgeons models where the cataractogenic insult was continuous, repeated administrations of pantethine and WR-77913 were necessary. The results suggested that protein aggregation and lens opacification associated with a variety of physiological and biochemical mechanisms can be delayed or inhibited using a systemic administration of pantethine or WR-77913. Topics: Amifostine; Animals; Cataract; Female; Galactose; Lens, Crystalline; Male; Pantetheine; Protein Denaturation; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Sodium Selenite; Streptozocin | 1996 |
Modulation of the chaperone-like activity of bovine alpha-crystallin.
The effects of pantethine, glutathione, and selected chemical reagents on the anti-aggregation activity of alpha-crystallin was evaluated. Protein aggregation was monitored by light scattering of solutions of denatured beta L-crystallin or alcohol dehydrogenase (ADH). The ratios of beta L-crystallin/alpha-crystallin and ADH/alpha-crystallin were adjusted so that partial inhibition of protein aggregation at 60 degrees C or 37 degrees C, respectively, was observed and modulation of the chaperone action of alpha-crystallin could be evaluated easily with selected endogenous metabolites. Enhancement of the anti-aggregation activity in the beta L-crystallin assay was strongest with pantethine, which appeared to interact with alpha-crystallin. Enhancement of the anti-aggregation activity in the ADH assay was strongest with glutathione which appeared to interact with ADH. The results indicated that the products of common metabolic pathways can modulate the chaperone-like effects of alpha-crystallin on protein aggregation. Topics: Alcohol Dehydrogenase; Animals; Cattle; Crystallins; Glutathione; Kinetics; Molecular Chaperones; Pantetheine; Protein Denaturation; Time Factors | 1996 |
Pantethine inhibits the formation of high-Tc protein aggregates in gamma B crystallin solutions.
Solutions of the bovine lens protein gamma B (or gamma II) crystallin at neutral pH in the absence of reducing agents, undergo a slow, partial conversion to a new protein species, gamma IIH. This species is an aggregate composed of an intermolecular, disulfide-crosslinked dimer (approximately equal to 32% of total protein by weight) and loosely associated dimers (approximately equal to 66%). gamma IIH has a phase separation temperature (Tph), at least 40 degrees C higher than that of native gamma II crystallin at any given protein concentration. In this paper we demonstrate that pantethine, a derivative of coenzyme A, inhibits the formation of gamma IIH.. gamma II crystallin solutions were incubated at pH 7.1 and room temperature with increasing amounts of pantethine. The Tph of the solutions was monitored as a function of incubation time. Corresponding to each Tph measurement, aliquots of each solution were analyzed by cation-exchange HPLC to determine the amount of gamma IIH formed.. Incubation of gamma II crystallin with increasing amounts of pantethine lowers Tph and suppresses the formation of gamma IIH. With pantethine to protein mole ratios of 0.66, 1 and 2, the Tph of gamma II crystallin is lowered from 8 degrees C in the native protein, to 2 degrees C, -3 degrees C respectively, at a protein concentration of approximately equal to 200 mg/ml. The amount of gamma IIH accumulated decreases from approximately 25% in the native protein to 10%, 1% and 0% respectively in these pantethine-treated protein solutions. For complete suppression of the rise in Tph and inhibition of gamma IIH formation, a 2:1 mole ratio of pantethine to protein is required.. We suggest that pantethine reacts with two cysteine residues of gamma IIH crystallin by forming a mixed disulfide, and effectively suppress protein aggregation and lowers Tph. This is due to the strong polar character of pantethine which reduces the net attractive interactions between the protein molecules. Topics: Animals; Animals, Newborn; Biopolymers; Cattle; Chromatography, Gel; Chromatography, High Pressure Liquid; Crystallins; Hydrogen-Ion Concentration; Lens, Crystalline; Pantetheine | 1996 |
Inhibition of lens opacification during the early stages of cataract formation.
To characterize the time period during cataract formation in which administration of pantethine inhibits lens cell opacification in the selenite model for cataract.. Pantethine was administered to neonatal rat pups at selected time points from -0.5 to 17 hours with respect to injection of selenite at time = 0. The injection dose of pantethine was 820 mg/kg (1.5 mmol/kg) diluted in water at 410 mg/ml concentration. The injection dose of selenite was 3.28 mg/kg (19 mumol/kg) diluted in saline at 1.8 mg/ml concentration. Opacification was observed using a slit lamp microscope at selected time points over a 14-day period. Cataracts were staged using a classification of opacity from 0 (normal) to 6 (mature).. The effect of pantethine was characterized by three different time periods: administration -0.5 to 6 hours with respect to selenite injection provided highly significant protection, P < 0.001; administration 8 hours after selenite provided significant protection, P < 0.005; administration 10 to 17 hours after selenite was not protective.. The metabolite pantethine inhibited lens opacification during cataract formation in the selenite model. Even when pantethine was injected several hours after the administration of selenite, opacification was inhibited. Advanced stages of opacification were unresponsive to the administration of pantethine. The inhibitory effect of pantethine was statistically significant when administered during the earliest stage of opacification in the selenite model for cataract. Topics: Animals; Animals, Newborn; Cataract; Disease Models, Animal; Female; Injections, Subcutaneous; Lens, Crystalline; Male; Pantetheine; Rats; Rats, Sprague-Dawley; Sodium Selenite; Time Factors | 1995 |
Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.
Preincubation of Ehrlich ascites tumor cells at 22 or 32 degrees C, but not at 0 degree C, with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine reduced lipid peroxidation (measured by production of thiobarbituric acid-reactive compounds) induced by the Fenton reaction (Fe2+ + H2O2) and partly protected the plasma membrane against the leakiness to cytoplasmic proteins produced by the same reagent. Pantothenic acid and its derivatives did not inhibit (Fe2+ + H2O2)-induced peroxidation of phospholipid multilamellar vesicles, thus indicating that their effect on the cells was not due to the scavenging mechanism. Homopantothenic acid and its 4'-phosphate ester (which are not precursors of CoA) neither protected Ehrlich ascites tumor cells against lipid peroxidation nor prevented plasma membrane leakiness under the same conditions. Incubation of the cells with pantothenic acid, 4'-phosphopantothenic acid, pantothenol, or pantethine significantly increased the amount of cellular CoA and potentiated incorporation of added palmitate into phospholipids and cholesterol esters. It is concluded that pantothenic acid and its related compounds protect the plasma membrane of Ehrlich ascites tumor cells against the damage by oxygen free radicals due to increasing cellular level of CoA. The latter compound may act by diminishing propagation of lipid peroxidation and promoting repair mechanisms, mainly the synthesis of phospholipids. Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Coenzyme A; Fatty Acids; Female; Ferrous Compounds; Hydrogen Peroxide; Lipid Peroxidation; Mice; Palmitic Acid; Palmitic Acids; Pantetheine; Pantothenic Acid; Thiobarbituric Acid Reactive Substances | 1995 |
Effects of pantethine on lipogenesis and CO2 production in the isolated hepatocytes of the chick (Gallus domesticus).
1. Isolated hepatocytes from chicks were used to study the effects of pantethine supplementation to incubation medium on in vitro lipogenesis, CO2 production and beta-oxidation of fatty acid. 2. In vitro lipogenesis, determined by the incorporation of 1-[14C]acetate into total lipid and various lipid fractions, as depressed in concordance with the increase of pantethine concentration in the medium. 3. Incubation of isolated hepatocytes with pantethine resulted in a significant decrease (P < 0.01) in the activities of acetyl-CoA carboxylase and fatty acid synthetase. 4. The results suggest that in vitro fatty acid synthesis from 1-[14C]acetate was depressed and CO2 production was elevated in hepatocytes of chicks through pantethine addition to the medium at a low level. Topics: Animals; Body Weight; Carbon Dioxide; Cell Survival; Cells, Cultured; Chickens; Fatty Acids; Lipids; Liver; Male; Organ Size; Oxidation-Reduction; Pantetheine | 1992 |
[Study of pantothenic acid derivatives as cardiac protectors in a model of experimental ischemia and reperfusion of the isolated heart].
An isolated heart model with experimental ischemia and reperfusion was used to show effective decrease in lactate, increase in ATP content and prevention of conjugated dienes accumulation in the myocardium by derivatives of pantothenic acid: panthenol (9.0 mg/kg), calcium pantothenate (15.6 mg/kg) and by these ones applied simultaneously as ingredients of perfusate (25 microM) in postischemic period. In that way derivatives of pantothenic acid should be regarded as cardiac protectors. Topics: Adenosine Triphosphate; Animals; Heart; In Vitro Techniques; Lactates; Lipid Peroxidation; Male; Myocardium; Pantetheine; Pantothenic Acid; Phosphocreatine; Rats; Rats, Wistar; Reperfusion Injury | 1992 |
[Comparison of the efficacy of pantethine, acipimox, and bezafibrate on plasma lipids and index of cardiovascular risk in diabetics with dyslipidemia].
Atherosclerotic manifestations are more common and precocious in diabetics than in the general population. Due to the increased cardiovascular risk, a primary or secondary (to diabetes mellitus) lipoprotein disorder in diabetics has to be carefully considered. 27 diabetics (15 NIDDM and 12 IDDM) with dyslipidemia (14 type IV, 8 type IIa and 5 type IIb) were divided in 3 groups and treated with 3 different hypolipemic drugs (Group A: pantethine 600 mg/day; Group B: acipimox 500 mg/day; Group C: bezafibrate 600 mg/day) to test their efficacy and acceptancy. Body weight, Hb A1-c, serum lipoproteins have been measured before and during the 6 months treatment. A significant variation of lipidemic pattern was observed in Group C: a decrease of cholesterol (-20%), triglycerides (-40%), LDL (-24.4%) and apo B (-26.8%) with an increase of HDL (+23.6%). Pantethine and acipimox were more effective on triglycerides (-37.7% and -23.3% respectively). Cardiovascular risk (CT tot/CT HDL) was significantly reduced with acipimox and normalized with bezafibrate. Topics: Bezafibrate; Cardiovascular Diseases; Diabetes Complications; Humans; Hyperlipidemias; Hypolipidemic Agents; Pantetheine; Pyrazines; Risk Factors | 1991 |
Effects of dietary pantethine levels on contents of fatty acids and thiobarbituric acid reactive substances in the liver of rats orally administered varying amounts of autoxidized linoleate.
The effects of dietary pantethine levels on the contents and compositions of fatty acids and on the levels of lipid peroxides were investigated with rat liver and its S-9 fraction under administration of 0 (non), 0.2 (low dose), and 0.35 ml (high dose) of autoxidized linoleate (AL) per 100 g body weight of the rats per day for 5 days. AL having 800 meq/kg of peroxide value (PV) and 1,700 meq/kg of carbonyl value (CV) was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (adequate), and 125 mg% pantethine (excess). In the pantethine-deficient and -adequate groups, the contents of fatty acids both in the liver homogenate and in the S-9 fraction were correspondingly decreased by increasing dose levels of AL, and the decrease was remarkable especially in the pantethine-deficient group, but was not significant in the pantethine-excess group even by a high dose of AL. Particularly, in the high dose of AL, the notable decreases of oleic acid (C18:1) contents in both the liver and the S-9 fraction were observed in rats of the pantethine-deficient and -adequate groups. The thiobarbituric acid (TBA) values in the liver homogenate and the S-9 fraction were increased correspondingly by increasing dose levels of AL, and the increases were repressed in the pantethine-excess group. Topics: Administration, Oral; Animals; Body Weight; Chromatography, Gas; Fatty Acids; In Vitro Techniques; Linoleic Acid; Linoleic Acids; Liver; Male; Malondialdehyde; Pantetheine; Rats; Rats, Inbred Strains; Thiobarbiturates | 1991 |
[Effects of pantethine on metabolism in myocardial mitochondria under the conditions of deep hypothermia].
Topics: Animals; Coenzyme A; Cytosol; Hypothermia; Malate Dehydrogenase; Male; Mitochondria, Heart; Oxidoreductases; Pantetheine; Rats; Rats, Inbred Strains | 1991 |
[Regulation of superoxide dismutase activity during deep hypothermia by simultaneous administration of water and lipid soluble antioxidants].
Alongside anti-hypoxia activity, the method of deep hypothermia causes discoordination of metabolism in the heart. This is due to increased secretion of catecholamines in the process of cooling, to activation in free radical generation and lipid peroxidation. Pantethine and alpha-tocopherol were used. Pantethine reduced lipid peroxidation, preserved reaction activity of catalyzing resyntheses and transport of high energetic compounds in the heart, while alpha-tocopherol prevented lipid peroxidation activation and decrease in SOD. Simultaneous use of pantethine and alpha-tocopherol caused increase in SOD and normalization of heart metabolism. Thus, for protection of the heart against excessive free radical generation under deep hypothermia simultaneous use of antioxidants like pantethine and alpha-tocopherol is necessary. Topics: Animals; Catecholamines; Hypothermia; Male; Myocardium; Pantetheine; Rats; Rats, Inbred Strains; Vitamin E | 1991 |
Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance.
Hyperlipemia is a very frequent complication of the diabetic patient on dialysis. There is difficulty of treatment with the diet, because the dietary restriction already imposed on these patients and the secondary effects and toxicity of the available drugs in uremics aggravate the problem. We have treated 22 diabetic patients on dialysis (8 on hemodialysis and 14 on continuous ambulatory peritoneal dialysis) suffering from hyperlipemia with pantethine, a physiological substance and coenzyme A precursor in the Krebs cycle. With the administration of an oral dose of 900 mg/day we obtained a reduction of total cholesterol (275 +/- 72 vs. 231 +/- 54 mg/dl; p less than 0.001), very-low-density lipoprotein (VLDL)-cholesterol (66 +/- 36 vs. 46 +/- 18 mg/dl; p less than 0.01) and triglycerides (332 +/- 182 vs. 227 +/- 90 mg/dl; p less than 0.01) at 2 months. High-density lipoprotein (HDL)-cholesterol did not change, but the total cholesterol/HDL-cholesterol ratio decreased significantly (p less than 0.05). Total cholesterol, VLDL and triglycerides showed a progressive and significant reduction at 4 and 6 months. No changes were observed in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, uric acid, blood glucose and glycosylated hemoglobin. Gastric discomfort in 2 patients and pruritus in another one were the secondary effects related. Pantethine was shown to be a very effective hypolipemic agent in diabetic patients on dialysis with a great tolerance. Topics: Cholesterol; Cholesterol, VLDL; Diabetic Nephropathies; Evaluation Studies as Topic; Female; Humans; Hyperlipidemias; Hypolipidemic Agents; Kidney Failure, Chronic; Male; Middle Aged; Pantetheine; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Triglycerides | 1991 |
[Effect of pantethine on post-heparin lipolytic activity and lipid peroxidation in the myocardium].
In the present work the effect of the precursor of Co a D-bis (N- pantothenyl-beta-aminoethyl) disulfide--pantethine on post heparin lipolytic activity and the intensity of lipid peroxidation has been investigated. Pantethine in doses of 5 mg/kg enhanced post heparin lipolytic activity (60.6%) and lipoprotein lipase activity (39.9%) in plasma and reduced the amount of NEFA (35.1%) and content of MDA (57.4%) in the mitochondria. Topics: Animals; Antioxidants; Enzyme Activation; Heparin; Hypolipidemic Agents; Lipid Metabolism; Lipid Peroxidation; Lipids; Lipoprotein Lipase; Male; Myocardium; Pantetheine; Rats; Rats, Inbred Strains | 1991 |
Dose- and time-response effects of pantethine on open-field behavior, and on central neurotransmission in rats.
In this study the dose- and time-related effects of pantethine on open-field behavior and central neurotransmissions were investigated in rats. Pantethine administered in low doses (0.48-0.96 mM/kg SC) only marginally influenced the activity of the animals, but induced a significant decrease of hypothalamic noradrenaline level without influencing the concentrations of dopamine and DOPAC. Injected in higher doses (1.95-3.90 mM/kg SC), the compound produced a marked depression of both open-field activity and noradrenaline levels, but increased the concentrations of dopamine and DOPAC in the hypothalamus. Twelve hr after the administration of the substance, its effect was attenuated, and 24 hr after the treatment neither the behavioral nor the monoamine parameters differed significantly from the control values. Concerning the somatostatin, pantethine administered in high doses (1.95-3.90 mM/kg SC) decreased the striatal concentration of somatostatin 4 hr after the injection, and this effect was attenuated 24 hr after the treatment. These data suggest that the pantethine-induced behavioral changes are correlated with its effect on central catecholaminergic and somatostatinergic transmission. Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Brain; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Exploratory Behavior; Hypothalamus; Male; Neurotransmitter Agents; Norepinephrine; Pantetheine; Radioimmunoassay; Rats; Rats, Inbred Strains; Somatostatin; Sulfhydryl Compounds; Time Factors | 1990 |
The depletion of plasma prolactin by pantethine in oestrogen-primed hyperprolactinaemic rats.
Pantethine was investigated for its potential to deplete prolactin in the plasma and pituitary cells of oestrogen-primed hyperprolactinaemic rats. This compound has been used in the past to deliver cysteamine systemically, through its congener pantetheine, a metabolic precursor for cysteamine. Cysteamine itself, specifically reduces plasma and pituitary prolactin. The addition of pantethine (2-10 mmol/l) to the media of isolated pituitary cells over 4 h did not appreciably alter the intracellular content of immunoreactive prolactin. Moreover, oral administration of pantethine at 0.5 and 1.0 g/kg body weight did not influence the concentration of immunoreactive plasma prolactin. However, the concentration of plasma prolactin fell by 48 and 67%, when pantethine was injected i.p. at 0.5 and 1.0 g/kg body weight, after 4 h. Intravenous administration of pantethine resulted in even greater losses of prolactin, in the order of 50 and 81% depletion for 0.5 and 1.0 g/kg body weight respectively and within 2 h of administration. However, cysteamine was found to be more efficacious than pantethine on a molar basis with regard to depleting the plasma concentration of prolactin in hyperprolactinaemic rats. Topics: Administration, Oral; Animals; Cysteamine; Estradiol; Hyperprolactinemia; In Vitro Techniques; Injections, Intraperitoneal; Injections, Intravenous; Male; Pantetheine; Pituitary Gland; Prolactin; Rats; Sulfhydryl Compounds | 1990 |
Protection by pantethine, pantothenic acid and cystamine against carbon tetrachloride-induced hepatotoxicity in the rat.
The daily ip administration of pantethine (500 mg/kg), pantothenic acid (100 mg/kg) or cystamine (50 mg/kg) for 5 days conferred significant protection against the hepatotoxic and peroxidative actions of a 0.5 mL/kg ip dose of CCl4 in rats. All three treatments lessened the increases in serum ALT and liver TBARS values, and the reductions in serum triglyceride levels, and prevented the development of hepatic steatosis caused by the halocarbon. Pantethine was found to offer the greatest protection. Topics: Alanine Transaminase; Animals; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cholesterol; Cystamine; Lipid Metabolism; Liver; Male; Pantetheine; Pantothenic Acid; Rats; Rats, Inbred Strains; Sulfhydryl Compounds; Triglycerides | 1990 |
[Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age].
Cardiovascular diseases are the main cause of death also in women. Their incidence, rapidly growing in the peri-menopausal period, is related to serum levels of total cholesterol and its LDL fraction. It was also shown that the peroxidation of LDL is an additional factor in the genesis of atherosclerotic vascular disease. As long-term treatments with synthetic lipid-lowering drugs may cause undesirable side effects, while pantethine is known to be well tolerated, we treated 24 hypercholesterolemic women (total serum cholesterol greater than or equal to 240 mg/dl), in perimenopausal age (range: 45-55 years, mean +/- SD = 51.6 +/- 2.4) with 900 mg/day of pantethine. This is a precursor of coenzyme A, with an antiperoxidation effect in vivo, and our aim was to confirm its lipid lowering activity in this particular type of patients. After 16 weeks of treatment, significant reductions of total cholesterol, LDL-cholesterol and LDL-C/HDL-C ratio could be observed. No remarkable changes of the main laboratory parameters (fasting blood sugar, B.U.N., creatinine, uric acid) were seen. Efficacy percentages of the treatment were about 80%. None of the patients complained of adverse reactions due to the treatment with pantethine. In conclusion, we suggest that pantethine should be considered in the long-term treatment of lipid derangements occurring in the perimenopausal age. Topics: Cholesterol, HDL; Cholesterol, LDL; Drug Evaluation; Female; Humans; Hypercholesterolemia; Menopause; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1990 |
Changes in oxytocin and vasopressin content in posterior pituitary and hypothalamus following pantethine treatment.
Pantethine, a cysteamine precursor, depletes somatostatin in the cerebral cortex and hypothalamus and prolactin in the anterior pituitary and hypothalamus. This study investigated the effect of pantethine on oxytocin and arginine vasopressin content in the posterior pituitary and hypothalamus. Male Long-Evans rats were injected intraperitoneally with escalating doses of pantethine (i.e., 146.7 mg, 293.4 mg and 586.6 mg/100 gm body weight). Hormone content was determined by radioimmunoassay. Three hours after pantethine treatment, the oxytocin content in the posterior pituitary and the hypothalamus was markedly reduced with all doses of the drug. Vasopressin content in the posterior pituitary and hypothalamus was decreased but to a lesser extent than oxytocin and only with the highest dose of pantethine. Pantethine may act to reduce oxytocin and vasopressin content through intracellular conversion to cysteamine. The exact mechanism of action of pantethine on oxytocin and vasopressin remains to be elucidated. Topics: Analysis of Variance; Animals; Hypothalamus; Male; Oxytocin; Pantetheine; Pituitary Gland, Posterior; Radioimmunoassay; Rats; Rats, Inbred Strains; Sulfhydryl Compounds; Vasopressins | 1990 |
[Pantethine, diabetes mellitus and atherosclerosis. Clinical study of 1045 patients].
After a review of the clinical studies on the treatment of diabetic patients with pantethine, the authors discuss the results obtained in a postmarketing surveillance (PMS) study on 1045 hyperlipidemic patients receiving pantethine (900 mg/day on average). Of these patients, 57 were insulin-dependent (Type I) and 241 were non insulin-dependent (Type II) diabetics. Beyond the epidemiological considerations made possible by a PMS study, the authors show that pantethine brought about a statistically significant and comparable improvement of lipid metabolism in the three groups of patients, with very good tolerability. Pantethine should therefore be considered for the treatment of lipid abnormalities also in patients at risk such as those with diabetes mellitus. Topics: Arteriosclerosis; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipoproteinemias; Male; Middle Aged; Pantetheine; Product Surveillance, Postmarketing; Sulfhydryl Compounds | 1989 |
Effects of cysteamine and pantethine on open-field behavior, hypothalamic catecholamine concentrations, and somatostatin-induced barrel rotation in rats.
Cysteamine administered in a dose of 1.95 mM/kg subcutaneously (SC) markedly reduced several open-field behaviors (locomotion, rearing, grooming and defecation), while pantethine, administered in an equimolar dose, reduced the locomotion only. However, administered in a dose of 3.90 mM/kg (SC), pantethine also markedly reduced all open-field parameters. Cysteamine, and to less extent pantethine, reduced noradrenaline, and increased dopamine and DOPAC concentrations in the hypothalamus. It is discussed whether the lower potency of pantethine on open-field behaviors and hypothalamic catecholaminergic neurotransmission is connected with the limited activity of pantetheinase, the cysteamine-generating enzyme. Intracerebroventricularly (ICV) administered somatostatin did not influence the pantethine-induced (1.95 mM/kg SC) behavioral changes in the open-field test. It is possible that the peptide did not reach at the receptor sites in a sufficient concentration because of the reduced endogenous somatostatin content, or that the pantethine-induced noradrenaline depletion is connected with the ineffectiveness of somatostatin. Furthermore, pretreatment with cysteamine (1.95 mM/kg SC) or pantethine (1.95 mM/kg or 3.90 mM/kg SC) attenuated the somatostatin-induced (10 micrograms ICV) barrel rotation, suggesting that the level of endogenous somatostatin may play a role in the pathogenesis of this motor disturbance. Topics: Animals; Cysteamine; Dose-Response Relationship, Drug; Drug Interactions; Hypothalamus; Male; Motor Activity; Pantetheine; Rats; Rats, Inbred Strains; Somatostatin; Stereotyped Behavior; Sulfhydryl Compounds | 1989 |
Effects of dietary pantethine levels on drug-metabolizing system in the liver of rats orally administered varying amounts of autoxidized linoleate.
The effects of dietary pantethine levels on the drug-metabolizing system were investigated under administration of varying amounts of autoxidized linoleate (AL) with rat liver microsomes and S-9 fractions. AL having 800 meq/kg of peroxide value and 1,700 meq/kg of carbonyl value was dosed to the rats of each group given drinking water containing 0 mg% (deficient), 6.25 mg% (normal), and 125 mg% pantethine (sufficient). The contents and activities of the enzymes in the drug-metabolizing system in the rat liver of each pantethine-level group changed essentially in a similar manner, that is, they were induced at an AL daily dose of 0.2 ml/100 g body weight (i.e., small dose) for 5 successive days and lowered at a daily dose of 0.4 ml/100 g body weight (i.e., large dose) by the same administration period, compared with respective non-AL groups in each of the three pantethine levels. In both non-AL and the small-dose AL, enzyme activities of the electron transfer system in rat liver microsomes, aminopyrine-N-demethylase activity, and metabolic activation of 2-acetylaminofluorene in S-9 fractions were significantly higher in the pantethine-deficient group than in the pantethine-normal and -sufficient groups. In the large-dose AL, the enzyme activities in the drug-metabolizing system decreased significantly in any pantethine levels, though the survival rate of the rats was higher in the pantethine-sufficient group than in the pantethine-normal groups. The results suggest that the pantethine relieves the effect of dosed AL on the drug-metabolizing system in rat liver. Topics: Animals; Cytochrome P-450 Enzyme System; Cytochromes b5; Diet; Dose-Response Relationship, Drug; Electron Transport; Growth; Linoleic Acid; Linoleic Acids; Liver; Male; Microsomes, Liver; Mixed Function Oxygenases; Oxidation-Reduction; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1989 |
Pantethine, a somatostatin depleting agent, increases food intake in rats.
During the course of studies of the effects of pantethine, a cysteamine precursor known to deplete tissue concentration of immunoreactive somatostatin, we observed that the subject rats continued to eat despite marked distension of the stomach. To determine whether this effect was caused by drug-altered food intake, we have measured food and water intake in pantethine-injected rats in the fed and fasting state. In three separate experiments, rats allowed free access to food until the morning of study showed significant increased food intake accompanied by an increased stomach content (at 4 hr) of both food and water following the IP injection of pantethine. In one experiment, intake at 3 hours was 0.60 g/100 g b.wt. (pantethine dose 0.74 g/kg b.wt.) and 0.64 g/100 g b.wt. (pantethine dose 1.47 g/kg b.wt.) compared with 0.24 g/100 g b.wt. in saline-treated animals (p less than 0.05). In contrast, pantethine, 1.47 g/kg b.wt., when administered to overnight-fasted rats, significantly inhibited food intake (3-hr intake 1.54 +/- 0.16 g/100 g b.wt. in rats injected with pantethine 1.47 g/kg b.wt. as compared with 3.3 +/- 0.21 g/100 g b.wt. in saline-injected controls). The intake-stimulating effect of pantethine in ad lib-fed rats was not demonstrable when the drug was administered shortly before the "lights out"-induced feeding at night. These findings indicate that pantethine, a cysteamine precursor, stimulates food intake in satiated rats, depending upon the stage of circadian rhythm, but is inhibitory to intake in fasted animals. We postulate that the effects are mediated directly or indirectly through the disinhibition of central appetite-regulating somatostatinergic pathways but, since cysteamine also inhibits dopamine-beta-hydroxylase, an effect on depletion of appetite-regulating central catecholamines cannot be excluded. Topics: Animals; Blood Glucose; Circadian Rhythm; Dose-Response Relationship, Drug; Drinking Behavior; Feeding Behavior; Food Deprivation; Male; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1989 |
Investigation of the roles of the substances in serum lipids and their constitutive fatty acids in chronic urticaria.
The newly-generated lipid mediators include products of arachidonate metabolism, prostaglandins and leukotrienes. In this study, serum lipids and fatty acids, including arachidonic acid (C20:4) were examined in 12 normal subjects (6 males and 6 females) and 23 subjects with chronic urticaria (6 males and 17 females), including 17 who made an excellent or good recovery (4 males and 13 females). The results indicated a relationship between chronic urticaria and serum lipids and fatty acids. The omega 6 (n-6) and omega 3 (n-3) series of polyunsaturated fatty acids and lipid peroxidation were suggested that may be one of the mediators in chronic urticaria. Pantethine, glutathione and ascorbic acid were effective in controlling chronic urticaria. Topics: Adult; Ascorbic Acid; Chronic Disease; Fatty Acids; Female; Glutathione; Humans; Lipids; Male; Middle Aged; Pantetheine; Urticaria | 1989 |
Modulation of HMG-CoA reductase activity by pantetheine/pantethine.
The ability of pantetheine/pantethine to modulate the activity of HMG-CoA reductase (EC 1.1.1.34) was determined in vitro with rat liver microsomes. The decay of the activity was obtained with pantethine in the 10(-5)-10(-4) M range, whereas stimulation by pantetheine occurred at 10(-3)-10(-2) M, as previously reported for GSSG and GSH, respectively. Inhibition of HMG-CoA by pantethine in isolated liver cells was also investigated by measuring the enzyme activity in microsomes isolated from hepatocytes incubated without or with 1 mM pantethine under conditions previously shown by us to induce inhibition of cholesterol synthesis from acetate. The enzyme amount was not modified by pantethine, but in cells treated with the disulphide, the relative amounts of the thiolic active forms of the enzyme, both phosphorylated and dephosphorylated, were decreased to about half compared to controls. Topics: Animals; Enzyme Activation; Glutathione; Hydroxymethylglutaryl CoA Reductases; Kinetics; Male; Microsomes, Liver; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1988 |
Lowering effect of pantethine on plasma beta-thromboglobulin and lipids in diabetes mellitus.
Pantethine in a dosage of 600 mg for the first 3 months, and in a dosage of 1200 mg for the second 6 months was given to 16 diabetics in whom plasma beta-thromboglobulin was raised (greater than 50 ng/ml). Plasma beta-TG levels decreased significantly with pantethine treatment for 9 months. Plasma triglyceride, total cholesterol, apo E and apo CII levels decreased significantly after 9 months. Plasma LDL-C and atherogenic index (LDL-C/HDL-C ratio or apo B/apo AI ratio) tended to decrease with treatment. It is concluded that administration of pantethine may be beneficial in the prevention of diabetic angiopathy because of its lowering effect on plasma beta-TG, lipids and apolipoproteins. Topics: Adult; Aged; beta-Thromboglobulin; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Hypoglycemic Agents; Hypolipidemic Agents; Lipids; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds | 1987 |
[Clinical use of pantethine by parenteral route in the treatment of hyperlipidemia].
Recent investigations have confirmed the effectiveness and the excellent tolerability of pantethine, a derivative of pantetheine, an essential part of the acetylation coenzyme CoA, administered P.O., in normalizing the blood lipid concentrations of patients with hyperlipidemias. A group of 18 patients with hyperlipidemias (9 M, 9 F), with an average age of 52.6 years, was submitted to pantethine parenteral treatment. After a 20 days wash-out, pantethine (400 mg/day; BID) was administered intramuscularly, for 20 days. Total cholesterol, triglycerides, HDL-cholesterol, apo A-1 and B lipoprotein, uric acid in serum, glycemia, CBC, B.U.N., creatininemia, E.S.R., SGOT, SGPT, bilirubinemia, cardiac frequency, blood pressure and body weight were controlled before and after treatment. The drug showed to have a therapeutic effectiveness by a rapid and significant improvement in the blood lipid pattern with reduction of total cholesterol, triglycerides and apo-B lipoprotein and increase of HDL-cholesterol and apo A-1 lipoprotein. The tolerability of pantethine at the stated dosage and mode of administration was invariably excellent, with non complaints or visible side effects imputable to the test drug. BUN, creatininemia, glycemia, SGOT, SGPT, bilirubinemia, E.S.R., CBC, cardiac frequency and blood pressure readings showed no noteworthy changes throughout the study. Topics: Cholesterol; Female; Humans; Hyperlipidemias; Infusions, Parenteral; Lipoproteins; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds | 1987 |
[Various hormonal parameters (ACTH, cortisol, somatotropic hormone and prolactin) following administration of a single high dose of pantethine in healthy subjects].
Topics: Adrenocorticotropic Hormone; Adult; Female; Growth Hormone; Humans; Hydrocortisone; Male; Pantetheine; Pituitary Gland, Anterior; Prolactin; Sulfhydryl Compounds | 1987 |
Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes.
The effects of pantethine on cholesterol and fatty acid metabolism were investigated in isolated rat hepatocytes. Preincubation of the cells with pantethine induced a concentration-dependent decrease of the radioactivity incorporated into carbon dioxide and lipids in incubations with [2-14C]acetate. When pantethine and the labeled substrate were simultaneously added to the cell suspension, there was an enhancement of carbon dioxide radioactivity at short incubation time (5 min) whereas, at longer incubation time, values were comparable to those of controls; lipid radioactivity, instead, was dramatically reduced by pantethine even at short incubation time and decreased further during the incubation, being 23% of that of controls at 60 min. Analysis of the incubation medium showed that pantethine induced a concentration- and time-dependent release of acetate into the medium. Results of the effect of the acetate concentration on the incorporation of [2-14C]acetate radioactivity into CO2 and lipids in control hepatocytes allowed the conclusion that the above-described modifications induced by pantethine are only partially attributable to the dilution of the labeled substrate, and that catabolism of acetate to carbon dioxide is stimulated by the disulphide pantethine, whereas cholesterol and fatty acid syntheses are inhibited. Topics: Animals; Carbon Dioxide; Cholesterol; Fatty Acids; In Vitro Techniques; Lipid Metabolism; Liver; Male; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1987 |
Effects of pantethine supplementation to diets with different energy cereals on hepatic lipogenesis of laying hens.
Effects on dietary pantethine supplementation on hepatic lipid accumulation and on the activities of lipogenic-related enzymes in the liver were studied in Single Comb White Leghorn laying hens fed isocaloric and isonitrogenous diets containing corn or barley as the carbohydrate source. Addition of 200 ppm pantethine to the corn-soy (CS) basal diet significantly reduced abdominal fat weight, liver triglyceride, as well as total cholesterol and 17 beta-estradiol concentrations in the plasma. Activities of citrate cleavage enzyme (EC 4.1.3.8; CCE) and fatty acid synthetase (FAS) in the liver were significantly reduced when the CS basal diet was supplemented with pantethine, but the activities of nicotinamide adenine dinucleotide phosphate-malate dehydrogenase (EC 1.1.1.40; NADP-MDH) and glucose-6-phosphate dehydrogenase (EC 1.1.1.49; G6PDH), were not significantly affected. However, liver triglyceride, total cholesterol, and 17 beta-estradiol concentrations in plasma as well as the activities of CCE, FAS, and NADP-MDH in liver were significantly lower in laying hens fed the barley-soy (BS) basal diet than in those fed the CS basal diet. Pantethine supplementation to the BS diet failed to show any significant effect on liver triglyceride content and on the hepatic activities of lipogenic-related enzymes. There were no significant differences in liver weight, rate of egg production, and egg weight among dietary treatments. these results suggest that dietary pantethine is effective in reducing the accumulation of liver and abdominal fat in laying hens fed a CS diet. Topics: Animal Nutritional Physiological Phenomena; Animals; Chickens; Edible Grain; Female; Lipid Metabolism; Liver; Oviposition; Pantetheine; Sulfhydryl Compounds | 1987 |
[Thrombocytopenic purpura during treatment with pantethine].
Topics: Aged; Female; Humans; Pantetheine; Purpura, Thrombocytopenic; Sulfhydryl Compounds | 1987 |
Pantethine lipomodulation: evidence for cysteamine mediation in vitro and in vivo.
Recent human studies suggest rapid in vivo hydrolysis of the lipid-lowering drug, pantethine, to the vitamin pantothenic acid and the small aminothiol compound, cysteamine. To test whether the active agent is a hydrolysis product, we repeated three experimental models of pantethine's effect with pantothenate and cysteamine. In vitro experiments with human fetal fibroblasts showed equivalent modulation of cholesterol and methyl sterol synthesis by pantethine, cysteamine, or cystamine (the disulfide of cysteamine), but pantothenate had no effect. Similarly, in vivo experiments with 0.5% cholesterol-fed rabbits showed oral pantethine or equimolar cystamine significantly lowered plasma cholesterol, while pantothenate, cystine, and 2-hydroxyethyl disulfide did not. Lastly, diabetic male rats (40 mg/kg streptozotocin) fed 0.1% pantethine and lower plasma free fatty acids after 2 weeks than controls, an effect not seen with pantothenate and largely duplicated by cystamine. The efficacy of pantethine has previously been attributed to altered vitamin metabolism and increased coenzyme A concentration. Pantethine did increase CoA levels 45% in rat liver homogenates while equivalent amounts of cystamine or pantothenate did not. However, a causal relationship between CoA levels and pantethine's action as a hypolipemic agent has never been shown. At least in 3 independent experimental models, the lipomodulating effect of pantethine appears instead to be mediated by the hydrolysis product cysteamine. Topics: Animals; Cells, Cultured; Coenzyme A; Cysteamine; Diabetes Mellitus, Experimental; Humans; Hydrolysis; Hypercholesterolemia; Lipid Metabolism; Male; Pantetheine; Rabbits; Rats; Sulfhydryl Compounds | 1987 |
Effectiveness of long-term treatment with pantethine in patients with dyslipidemia.
A one-year clinical trial with pantethine was conducted in 24 patients with established dyslipidemia of Fredrickson's types II A, II B, and IV, alone or associated with diabetes mellitus. The treatment was well tolerated by all patients with no subjective complaints or detectable side effects. Blood lipid assays repeated after 1, 3, 6, 9, and 12 months of treatment revealed consistent and statistically significant reductions of all atherogenic lipid fractions (total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B) with parallel increases of high-density lipoprotein cholesterol and apolipoprotein A. The results were equally good in patients with uncomplicated dyslipidemia and in those with associated diabetes mellitus. The authors conclude that pantethine (a drug entity related to the natural compound, pantetheine) represents a valid therapeutic support for patients with dyslipidemia not amenable to satisfactory correction of blood lipids by diet alone. Topics: Cholesterol; Female; Humans; Hyperlipidemias; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Long-Term Care; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1986 |
Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.
Following a brief outline of current knowledge concerning atherosclerosis and its treatment, the authors describe the results obtained by treating with pantethine (900-1200 mg daily for 3 to 6 months) a series of 7 children and 65 adults suffering from hypercholesterolemia alone or associated with hypertriglyceridemia (types IIa and IIb of Fredrickson's classification). Pantethine treatment produced significant reduction of the better known risk factors (total cholesterol, LDL-cholesterol, triglycerides, and apo-B) and a significant increase of HDL-cholesterol (signally HDL2) and apolipoprotein A-I. The authors conclude with a discussion of these results and of the possible role of pantethine in the treatment of hyperlipoproteinemia, in view of its perfect tolerability and demonstrated therapeutic effectiveness. Topics: Adolescent; Adult; Aged; Apolipoprotein A-I; Apolipoproteins A; Apolipoproteins B; Child; Cholesterol; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II; Lipoproteins; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1986 |
Activation and inhibition of yeast aldehyde dehydrogenase activity by pantethine and its metabolites.
D-Pantethine-related metabolites, such as taurine, D-pantetheine, coenzyme A and D-pantothenate, activated yeast aldehyde dehydrogenase in vitro. D-Pantethine and cysteamine hydrochloride, however, strongly inhibited the activity of this enzyme. Topics: Acetyl Coenzyme A; Aldehyde Dehydrogenase; Coenzyme A; Cysteamine; Enzyme Activation; Pantetheine; Pantothenic Acid; Saccharomyces cerevisiae; Sulfhydryl Compounds; Taurine | 1986 |
Enzymatic hydrolysis of pantetheine.
Topics: Amidohydrolases; Animals; Carbon Radioisotopes; Chromatography, Paper; Electrophoresis, Polyacrylamide Gel; GPI-Linked Proteins; Indicators and Reagents; Kidney; Kinetics; Male; Pantetheine; Radioisotope Dilution Technique; Rats; Sulfhydryl Compounds; Swine; Tissue Distribution | 1986 |
Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes.
Results presented here show that when isolated rat hepatocytes are incubated with increasing concentrations of [2-14C]mevalonolactone, incorporation of the substrate into cholesterol is progressively reduced. Correspondingly, an increase of the incorporation of the substrate into precursors of cholesterol (methyl sterols and squalene) occurs. These effects and the observed inhibition of HMGCoA reductase at high mevalonolactone concentration (0.5 mM) are in agreement with those shown by others in cultured hepatocytes. Since pantethine was reported to affect cholesterol biosynthesis from mevalonate in cultured fibroblasts, effects of its addition to hepatocyte incubations at low and high mevalonolactone concentration were studied. Neither the amount of radioactivity incorporated into cholesterol and in its sterol precursors nor sterol levels were modified by pantethine when a mevalonolactone concentration (0.01 mM) that did not alter the levels of intermediates of cholesterol synthesis was used. Pantethine was shown instead to potentiate the decrease of mevalonate incorporation into cholesterol induced by high concentrations of mevalonolactone (0.5 mM). Decrease of 3-hydroxy-3-methylglutaryl CoA reductase activity induced by 1 mM pantethine was twice that caused by mevalonolactone alone. These results may explain the fact that both in laboratory animals and in humans pantethine administration is effective in reducing cholesterol plasma levels in hyperlipidemic conditions. Topics: Animals; Carbon Radioisotopes; Cholesterol; Cholesterol 7-alpha-Hydroxylase; Hydroxymethylglutaryl-CoA Reductase Inhibitors; In Vitro Techniques; Liver; Male; Mevalonic Acid; Pantetheine; Rats; Rats, Inbred Strains; Squalene; Sterol O-Acyltransferase; Sulfhydryl Compounds | 1986 |
Effect of probucol, pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in the rabbit.
Effect of probucol, pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in aorta and coronary artery was studied in cholesterol-fed rabbits. Probucol treatment (0.5% in diet) resulted in reducing HDL cholesterol and serum apo A-I levels significantly, while pantethine treatment (0.25%-0.75% in diet) tended to increase HDL cholesterol and serum apo A-I levels. Combined treatment with these two drugs showed a significant prevention in the reduction of HDL cholesterol and serum apo A-I levels by probucol alone. Probucol or pantethine treatment reduced effectively (V) LDL cholesterol and serum apo B levels, and these effects were accelerated additively when the two drugs were given concurrently. Atheromatous lesions in aorta and coronary artery in cholesterol-fed rabbits were prevented by the treatment with probucol (0.5% in diet) or pantethine (0.75% in diet) for 24 weeks. The combined treatment with these two drugs showed more marked prevention than either drug alone. From these findings, it is concluded that the combined treatment of probucol with pantethine is effective for improvement of serum lipoprotein disorders and for prevention of the incidence of atheromatous lesions in aorta and coronary artery in cholesterol-fed rabbits. Topics: Animals; Apolipoproteins; Arteriosclerosis; Cholesterol, HDL; Drug Synergism; Lipoproteins; Male; Pantetheine; Phenols; Probucol; Rabbits; Sulfhydryl Compounds | 1986 |
[Studies on percutaneous absorption of pantethine in guinea pigs].
Topics: Animals; Autoradiography; Guinea Pigs; Male; Pantetheine; Skin Absorption; Sulfhydryl Compounds | 1986 |
Pantethine, a cysteamine precursor, depletes immunoreactive somatostatin and prolactin in the rat.
Pantethine, a stable disulfide precursor of pantetheine, has been reported to increase intracellular concentration of cysteamine in cultured fibroblasts of patients with cystinosis. In order to determine whether pantethine acts like cysteamine in bringing about depletion of immunoreactive somatostatin (IRS) in rat neural and gastrointestinal tissues and depletion of immunoreactive PRL (IRPRL) in the anterior pituitary, groups of male rats were given pantethine by ip injection at a dose of 0.264 mM or 0.528 mM/100 g body weight or normal saline and killed 4 h later. The interval chosen corresponds to the time of maximum effect after oral cysteamine administration. In cerebral cortex, hypothalamus, duodenal and gastric mucosa, and pancreas, IRS was uniformly depressed by 50% or more as compared with control rats, the most striking changes occurring in the hypothalamus where there was a 64% depletion at the higher dose of drug. Both dosage levels depleted IRPRL in pituitary and serum. At the higher dose, IRPRL was reduced by approximately 85% in the pituitary and 75% in the serum. These findings support the hypothesis that pantethine administration leads to an accumulation of cysteamine within cells throughout the body and that the cysteamine so formed depletes IRS and IRPRL. Topics: Animals; Cerebral Cortex; Duodenum; Gastric Mucosa; Hypothalamus; Intestinal Mucosa; Kinetics; Male; Pancreas; Pantetheine; Prolactin; Radioimmunoassay; Rats; Rats, Inbred Strains; Somatostatin; Sulfhydryl Compounds; Tissue Distribution | 1985 |
The effects of pantethine on lipid and lipoprotein abnormalities in survivors of cerebral infarction.
A daily 1000 mg of pantethine was orally administered to 12 male survivors of cerebral infarction for 3 months. Before and after the medication, plasma lipoproteins were ultracentrifugally separated. Plasma concentrations of total cholesterol, triglyceride, phospholipid, and VLDL- and LDL-cholesterol tended to decrease. On the contrary, HDL-cholesterol concentration and HDL:LDL-cholesterol ratio significantly increased. HDL2-cholesterol concentration significantly increased, whereas HDL3-cholesterol concentration remained unchanged, resulting in a significant elevation of HDL2:HDL3-cholesterol ratio. In HDL2 the percentage content of cholesterol and triglyceride decreased, while that of phospholipid increased. However, no significant changes were found in the chemical composition of HDL3. The plasma concentrations of apo A-I and, to a lesser extent, A-II increased, with a slight increase in A-I:A-II ratio but A-I:A-II ratio in either HDL2 or HDL3 remained unchanged. Topics: Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Cerebral Infarction; Cholesterol; Humans; Lipids; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Pantetheine; Phospholipids; Sulfhydryl Compounds; Triglycerides | 1985 |
Effects of pantethine on action potential of canine papillary muscle during hypoxic perfusion.
Pantethine, which is known to be converted to coenzyme A, has been reported to have antiarrhythmic action on experimental cardiac arrhythmias. Using standard microelectrode techniques, the electrophysiological effects of pantethine under hypoxic (95% N2 + 5% CO2) perfusion were studied. Hypoxia decreased resting membrane potential, action potential amplitude and maximum velocity of phase 0 and shortened action potential duration and effective refractory period. Application of pantethine 5 X 10(-3) Gm/ml under hypoxic perfusion prolonged action potential duration and effective refractory period significantly. Prolongation of action potential duration by pantethine might be caused by an increase in intracellular ATP. The findings in this study could be an explanation of the possible antiarrhythmic effects of pantethine. Topics: Action Potentials; Animals; Dogs; Electrophysiology; In Vitro Techniques; Membrane Potentials; Microelectrodes; Oxygen; Pantetheine; Papillary Muscles; Perfusion; Refractory Period, Electrophysiological; Sulfhydryl Compounds | 1985 |
[Effects of D(+)-bis-(N-pantothenyl-amidoethyl)-disulphur on the blood lipid profile and apoproteins A and B levels].
Topics: Adult; Apolipoproteins A; Apolipoproteins B; Cholesterol, HDL; Female; Humans; Lipids; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds; Triglycerides | 1985 |
Metabolism of pantethine in cystinosis.
D-Pantethine is a conjugate of the vitamin pantothenic acid and the low-molecular-weight aminothiol cysteamine. Pantethine is an experimental hypolipemic agent and has been suggested as a source of cysteamine in the treatment of nephropathic cystinosis. We treated four cystinotic children with 70-1,000 mg/kg per d oral D-pantethine and studied its metabolism. Pantethine was rapidly hydrolyzed to pantothenic acid and cysteamine; we could not detect pantethine in plasma after oral administration. The responsible enzyme, "pantetheinase," was highly active in homogenates of small intestinal mucosa and plasma. The Michaelis constant of the rat intestinal enzyme was 4.6 microM and its pH profile showed a broad plateau between 4 and 9. Pantothenate pharmacokinetics after orally administered pantethine followed an open two-compartment model with slow vitamin elimination (t1/2 = 28 h). Peak plasma pantothenate occurred at 2.5 h and levels over 250 microM were seen at 300 times normal. Apparent total body storage of pantothenate was significant (25 mg/kg), and plasma levels were elevated threefold for months after pantethine therapy. Plasma cysteamine concentrations after pantethine were similar to those reported after equivalent doses of cysteamine. However, at best only 80% white blood cell cystine depletion occurred. We conclude that pantethine is probably less effective than cysteamine in the treatment of nephropathic cystinosis and should only be considered in cases of cysteamine intolerance. Serum cholesterol was decreased an average of 14%, which supports the potential clinical significance of pantethine as a hypolipemic agent. Rapid in vivo hydrolysis of pantethine suggests that pantothenate or cysteamine may be the effectors of its hypolipemic action. Topics: Adolescent; Amidohydrolases; Animals; Child; Cysteamine; Cystine; Cystinosis; Diarrhea; Female; GPI-Linked Proteins; Humans; Intestinal Absorption; Intestinal Mucosa; Kinetics; Leukocytes; Male; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1985 |
Changes in fatty acid composition of the single platelet phospholipids induced by pantethine treatment.
In a single-blind cross-over study the effect of oral treatment with pantethine on plasma and platelet lipid composition was evaluated in 20 patients with dyslipidaemia (7 IIa, 7 IIb and 6 Iv type). In plasma significant decreases of total cholesterol and triglycerides with increase of high density lipoprotein-cholesterol were observed. In platelets pantethine treatment significantly reduced phospholipid and cholesterol content. In addition gas-chromatographic analysis showed a reduction of saturated and monounsaturated and a relative increase of polyunsaturated fatty acid content of platelet phospholipids. A selective relative increase was observed of some n-3 polyunsaturated fatty acids like eicosapentaenoic and docosahexaenoic acid whereas arachidonic acid decreased. The present study indicates a favourable influence of pantethine not only on plasma but also on platelet lipids which could be of value in delaying the development of atherosclerosis in dyslipidaemic patients. Topics: Administration, Oral; Adult; Aged; Blood Platelets; Cholesterol; Cholesterol, HDL; Chromatography, Gas; Fatty Acids; Female; Humans; Hyperlipoproteinemia Type II; Hyperlipoproteinemia Type IV; Male; Middle Aged; Pantetheine; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Sulfhydryl Compounds; Triglycerides | 1985 |
Therapy of cystinosis.
Topics: Cysteamine; Cystinosis; Humans; Orphan Drug Production; Pantetheine | 1985 |
Effects of pantethine on in-vitro peroxidation of low density lipoproteins.
The effects of pantethine on LDL peroxidation in vitro are reported. LDL isolation by density gradient ultracentrifugation from 12 normal subjects were dialyzed 48 h under conditions allowing oxidation. The LDL peroxides were assayed for the presence of malondialdehyde (MDA) on the lipoprotein. The effect of peroxidation on the LDL protein moiety (apo B) was studied by SDS-gel electrophoresis. The presence in the dialysis buffer of 1 mM reduced glutathione or of an equimolar concentration of pantethine markedly inhibited the MDA formation in LDL. Less effective were 0.5 and 2 mM pantethine, while 10 mM pantethine did not prevent the LDL peroxidation. Both glutathione and pantethine (1 or 2 mM) preserved the original LDL electrophoretic mobility. The electronegative charge of LDL was correlated to the MDA production during the dialysis procedures. Freshly prepared LDL showed a single apo B band by SDS-gel electrophoresis (apo B-100). Following peroxidation 2 or 3 bands with higher molecular weight appeared. Both glutathione and pantethine (1 or 2 mM) strongly inhibited the appearance of higher molecular weight peptides. In appropriate concentrations therefore pantethine inhibits the LDL peroxidation in vitro, thus preserving the molecular integrity of apo B. Topics: Antioxidants; Apolipoproteins B; Dialysis; Glutathione; Humans; In Vitro Techniques; Lipid Peroxides; Lipoproteins, LDL; Male; Malondialdehyde; Molecular Weight; Pantetheine; Sulfhydryl Compounds | 1985 |
[Therapeutic use of a combination containing calcium, vitamins, pantethine and carnitine in convalescence states in childhood].
Topics: Calcium; Carnitine; Child; Child, Preschool; Convalescence; Drug Combinations; Female; Humans; Infant; Male; Pantetheine; Sulfhydryl Compounds; Vitamins | 1985 |
Macrophage activation with pantethine and pantetheine-4'-phosphate.
Adjuvant activities of pantethine (PaSS) and pantetheine-4'-phosphate (PSH-4'-P) were investigated in mice. By the multiple intraperitoneal administration, both PaSS and PSH-4'-P activated the functions of mouse peritoneal adherent cells and splenic natural killer cells. PSH-4'-P was also effective for the activation of natural killer cells by single injection. In in vitro, PaSS induced interleukin-1 (IL-1) secretion at a low concentration but PSH-4'-P did not. Both PaSS and PSH-4'-P could neither induce interleukin-2 (IL-2) secretion, nor could enhance IL-2 secretion by Con A. Topics: Animals; Cells, Cultured; Cytotoxicity, Immunologic; Female; Kinetics; Macrophage Activation; Macrophages; Mice; Mice, Inbred C57BL; Pantetheine; Structure-Activity Relationship; Sulfhydryl Compounds | 1985 |
Pantetheine and pantethine esters with hypolipidemic nicotinic acid derivatives.
We prepared several esters of pantetheine and pantethine, respectively, with 3-pyridineacetic acid and with 3-(3-pyridinemethoxycarbonyl)propionic acid, and we tested these products for their capacity to lower serum non-esterified fatty acids and triglycerides in normal animals. Among the products thus tested, the tetraester of pantethine with 3-(3-pyridinemethoxycarbonyl)propionic acid (MG 28362) displayed marked hypolipidemic activity, the action being of uncommonly long duration. Topics: Animals; Chemical Phenomena; Chemistry; Fatty Acids, Nonesterified; Hypolipidemic Agents; Male; Nicotinic Acids; Pantetheine; Rats; Rats, Inbred Strains; Spectrophotometry, Ultraviolet; Sulfhydryl Compounds; Triglycerides | 1985 |
[Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine].
The hypolipidemizing effects of Pantethine were investigated by the Authors in 37 hypercholesterolemic and/or hypertriglyceridemic patients. Of these, 21 were also diabetic, in a satisfying glucidic compensation, in order to verify the action of this drug also in this metabolic condition. The study was carried out for three months and during this period the patients were given Pantethine at the dose of 600 mg/die orally. At the 30th, the 60th, the 90th day of treatment the following parameters were controlled: cholesterolemia, HDL cholesterol, apolipoproteins A and B, triglyceridemia, systolic and diastolic arterial pressure, uricemia, body weight. Thirty days after suspending the treatment, the parameters were controlled again to detect a possible "rebound" effect. The results were analyzed on the whole case-record, subdividing the patients in dislipidemic and diabetic-dislipidemic, and on the basis of the Fredrickson's classification. Pantethine induced in all groups a quick and progressive decrease of cholesterolemia, triglyceridemia, LDL cholesterol and Apolipoproteins B with increased HDL cholesterol and Apolipoproteins A. After suspending the treatment, there is a clear inversion of the state of these parameters. The Authors conclude that the present work shows that Pantethine, a natural and atoxic substance, an important component of Coenzyme A, is efficacious in determining a clear tendency towards normalization of the lipidic values. Topics: Adolescent; Adult; Aged; Apolipoproteins; Arteriosclerosis; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Complications; Female; Humans; Hypercholesterolemia; Hyperlipoproteinemias; Lipoproteins, HDL; Lipoproteins, LDL; Male; Middle Aged; Pantetheine; Sulfhydryl Compounds | 1984 |
[Treatment of chronic hepatopathies with phosphorylcholine and pantethine].
Topics: Adult; Aged; Choline; Chronic Disease; Drug Combinations; Female; Humans; Liver Diseases; Male; Middle Aged; Pantetheine; Phosphorylcholine; Sulfhydryl Compounds | 1984 |
Pantethine reduces plasma cholesterol and the severity of arterial lesions in experimental hypercholesterolemic rabbits.
Pantethine (P), a coenzyme A precursor, was administered to cholesterol-fed rabbits (0.5% cholesterol diet + 1% pantethine) for 90 days. At the end of treatment, plasma total cholesterol levels were reduced 64.7% and the HDL/total cholesterol ratio increased in P-treated animals; a significant rise of the apo A-I/A-II ratio was detected in HDL. VLDL lipid and protein levels were, on the other hand, reduced by P. The cholesterol-ester content of both liver and aortic tissues was not significantly affected by P. Although the total aortic area with evident plaques was reduced only 18.2%, the microscopical examination of sections from the major vessels of P-treated animals, showed a reduction in the severity of lesions, both in the aorta and in the coronary arteries. These findings suggest that P, in addition to significantly lowering plasma cholesterol levels in rabbits on an experimental diet, may modify lipid deposition in major arteries, possibly by affecting lipoprotein composition and/or exerting an arterial protective effect. Topics: Animals; Aorta, Abdominal; Apolipoprotein A-I; Apolipoprotein A-II; Apolipoproteins A; Cholesterol, Dietary; Cholesterol, HDL; Coronary Vessels; Hypercholesterolemia; Isoelectric Focusing; Lipoproteins, HDL; Male; Pantetheine; Rabbits; Sulfhydryl Compounds | 1984 |
Pantethine and pantothenate effect on the CoA content of rat liver.
The role of pantethine as a precursor of CoA in rat liver has been examined. It has been demonstrated that pantethine induces a significant increase in the total CoA content both in perfused liver and in liver homogenate, while it fails to affect the mitochondrial CoA content when added to isolated mitochondria. Pantethine is more efficient than pantothenate in inducing the synthesis of CoA in rat liver, even in the presence of added cysteine. The possible metabolic implications are discussed. Topics: Animals; Coenzyme A; Cysteine; In Vitro Techniques; Liver; Male; Mitochondria, Liver; Pantetheine; Pantothenic Acid; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1984 |
[Effect of oral pantethine administration on blood acetaldehyde levels following alcohol ingestion].
Topics: Acetaldehyde; Administration, Oral; Adult; Alcohol Drinking; Humans; Male; Pantetheine; Sulfhydryl Compounds | 1984 |
Renal cell culture using autopsy material from children with cystinosis.
Renal cell cultures were initiated using fresh autopsy material from two individuals with cystinosis, ages 5 and 8 yr. Cells obtained from collagenase treated autopsy material were grown in a selective kidney medium containing Coon's modified F12, 2.5% fetal bovine serum, transferrin, insulin, selenium, hydrocortisone, PGE1, and fibronectin. These cells had an epithelial appearance, formed domes, and were periodic acid-Schiff positive. Both tight junctions and microvilli were seen by electron microscopy. Fibroblasts had a cloning efficiency of zero in the selective medium and grew poorly compared to their growth in Coon's F12 with 10% fetal bovine serum. The lysosomal cystine content of the renal cells was greatly elevated and comparable to that of fibroblasts from cystinotic patients. Renal cell lysosomal cystine levels were only partially reduced by exposure to either pantethine or the aminothiol, cysteamine. However, exposure to either compound effectively depleted cystinotic cultured fibroblasts of their lysosomal cystine. Study of cultured renal material may have practical significance in pharmacologic considerations. Topics: Autopsy; Cells, Cultured; Child, Preschool; Cysteamine; Cystine; Cystinosis; Fibroblasts; Humans; Kidney; Male; Pantetheine | 1984 |
Effect of pantethine on post-heparin plasma lipolytic activities and adipose tissue lipoprotein lipase in rats.
The lipid-lowering effect of pantethine, a new drug affecting lipid metabolism, had been evaluated in carbohydrate-induced hyperlipidemic rats. Administration of the drug raised post-heparin lipolytic activities, the change being due to an increase in lipoprotein lipase activity, whereas hepatic lipase activity remained virtually unchanged. Total lipoprotein lipase activity per g of adipose tissue increased in pantethine-treated rats compared with controls. Furthermore, the soluble lipoprotein lipase of fat-pads was fractionated by heparin-Sepharose affinity chromatography. The first active peak, originated from the microsomal fractions, significantly increased after the drug treatment, while the second one, originated from the plasma membranes, remained unchanged. The increase in the microsomal lipoprotein lipase activity may be due to an increase in intracellular synthesis of lipoprotein lipase enzyme proteins. The heterogeneity of lipoprotein lipase of rat adipose tissues was ensured using affinity chromatography on heparin-Sepharose. Topics: Adipose Tissue; Animals; Body Weight; Chromatography, Agarose; Epididymis; Hyperlipidemias; Lipids; Lipoprotein Lipase; Liver; Male; Organ Size; Pantetheine; Rats; Rats, Inbred Strains; Sepharose; Subcellular Fractions; Sulfhydryl Compounds | 1984 |
Pantethine and cystamine deplete cystine from cystinotic fibroblasts via efflux of cysteamine-cysteine mixed disulfide.
Children suffering from cystinosis, a genetic disease characterized by high levels of lysosomal cystine, are currently being treated with cysteamine to lower the cystine levels in their cells. In fibroblasts from these patients, cysteamine and its disulfide, cystamine, are equally effective in lowering cystine levels. We recently reported that pantethine, a dietary precursor of coenzyme A, depletes cystine from cultured, cystinotic fibroblasts as effectively as cystamine. To determine the mechanism of action of pantethine, and of cystamine, we have compared the fate of [35S]cystine-derived metabolites in the presence and absence of these agents. The results indicate that the ability of pantethine to deplete cystine resides in its being a metabolic precursor of cysteamine. Furthermore, both pantethine and cystamine act by generating the mixed disulfide of cysteamine and cysteine in the lysosomes, which is then rapidly excreted from the cells. The fall in intracellular [35S]cystine caused by these agents was not accompanied by a comparable increase in any intracellular metabolite; rather, it could be accounted for by the appearance of mixed disulfide in the medium. There was no accumulation of mixed disulfide in the cells. Radioactivity in cytoplasmic glutathione was, however, increased by cystamine or pantethine. Thus, cysteamine (formed intracellularly in these experiments) undergoes thiol-disulfide exchange with cystine in the lysosomes, producing cysteamine-cysteine mixed disulfide and free cysteine, which enter the cytoplasm. The free cysteine is available to several pathways, including oxidation to the disulfide or the mixed disulfide, and synthesis of glutathione. The mixed disulfide is excreted from the cell, which ultimately depletes the cell of its excess cystine. Topics: Cells, Cultured; Child; Cystamine; Cystine; Cystinosis; Fibroblasts; Humans; Kinetics; Pantetheine; Skin; Sulfhydryl Compounds | 1984 |
Effects of pantethine and its metabolites on fatty acid oxidation in rat liver mitochondria.
The mechanism of the activating effect of pantethine [D-bis-(N-pantothenyl-beta-aminoethyl)disulfide] on fatty acid oxidation was investigated in rat liver mitochondria. Pantethine, pantetheine and 4'-phosphopantetheine activated three steps of fatty acid oxidation, i.e., acyl-CoA synthetase, carnitine, acyltransferase and intramitochondrial oxidation, to various extents. Although their effects may have been partly due to CoASH derived from them, they also had specific effects. Topics: Acyl Coenzyme A; Animals; Carnitine Acyltransferases; Coenzyme A Ligases; Fatty Acids; In Vitro Techniques; Male; Mitochondria, Liver; Oxidation-Reduction; Pantetheine; Rats; Rats, Inbred Strains; Repressor Proteins; Saccharomyces cerevisiae Proteins; Sulfhydryl Compounds | 1983 |
Effect of pantethine on fatty acid oxidation in microvessels of rat brain.
Fatty acid oxidation in brain microvessels decreased greatly when persistent hypertension developed in spontaneously hypertensive rats (SHR). Treatment of SHR with pantethine [D-bis-(N-pantothenyl-beta-aminoethyl) disulfide] in vivo for 4 weeks restored their fatty acid oxidation activity to the control level. The mechanism of the activating effect of pantethine on fatty acid oxidation was investigated in brain microvessels. Pantethine and its metabolites (pantetheine and 4'-phosphopantetheine) activated three steps of fatty acid oxidation, i.e., acyl-CoA synthetase, carnitine acyltransferase and intramitochondrial oxidation. The relation between changes in fatty acid oxidation activities and injuries of brain microvessels and the protective effect of pantethine against such injuries is discussed. Topics: Animals; Brain; Cerebral Hemorrhage; Fatty Acids; Hypertension; In Vitro Techniques; Microcirculation; Pantetheine; Rats; Sulfhydryl Compounds | 1983 |
Pantethine depletes cystinotic fibroblasts of cystine.
Topics: Cells, Cultured; Cystamine; Cystine; Cystinosis; Dose-Response Relationship, Drug; Fibroblasts; Humans; Pantetheine; Sulfhydryl Compounds | 1983 |
Positive inotropic and negative chronotropic effect of pantethine on isolated cardiac muscle of guinea-pigs.
It was demonstrated that pantethine, a component of co-enzyme A, produces positive inotropic and negative chronotropic actions in isolated cardiac muscle preparations from guinea-pigs. Topics: Animals; Depression, Chemical; Guinea Pigs; Heart Atria; Heart Rate; Myocardial Contraction; Pantetheine; Stimulation, Chemical; Sulfhydryl Compounds | 1983 |
Effect of pantethine on lipoprotein profiles and HDL subfractions in experimentally hypercholesterolemic rabbits.
A high-cholesterol diet caused in rabbits a great increase in beta-migrating VLDL and a significant decrease in HDL 2 (43% of normal) and HDL 3 masses (64% of normal), without significant changes in HDL cholesterol values. Chemical analysis of the HDL subfractions indicated an abnormal lipid-protein composition in the hypercholesterolemic rabbits, an increase in cholesterol and a decrease in the contents of triglycerides and phospholipid. When these rabbits were treated for about 1 month with pantethine, and intermediate precursor of coenzyme A, the increase in cholesterol levels was effectively prevented in the beta-VLDL (11%) and LDL fractions (43%) but, conversely, HDL-cholesterol was significantly increased (151%). In a separate experiment, HDL 2 and HDL 3 masses were calculated to be increased to 186% and 193%, respectively, by pantethine treatment, when compared with those in control cholesterol-fed rabbits. Serum apolipoprotein AI antigen levels were also significantly increased by the treatment. Topics: Animals; Cholesterol, Dietary; Hypercholesterolemia; Lipoproteins; Lipoproteins, HDL; Male; Pantetheine; Rabbits; Sulfhydryl Compounds | 1982 |
Effect of pantethine on myocardial pH reduced by partial occlusion of the coronary artery in dogs with special reference to the myocardial levels of adenosine triphosphate, creatine phosphate, and lactate.
Topics: Adenosine Triphosphate; Animals; Coronary Disease; Dogs; Female; Hemodynamics; Hydrogen-Ion Concentration; Lactates; Lactic Acid; Male; Myocardium; Oxygen Consumption; Pantetheine; Phosphocreatine; Sulfhydryl Compounds; Time Factors | 1982 |
Effects of pantethine on different models of experimental hyperlipidemia in rodents: a comparison with clofibrate.
Topics: Animals; Clofibrate; Disease Models, Animal; Hyperlipidemias; Hypolipidemic Agents; Lipoproteins, HDL; Male; Pantetheine; Rats; Sulfhydryl Compounds | 1982 |
Effect of pantethine on the biosynthesis of cholesterol in human skin fibroblasts.
Pantethine [D-bis-(N-pantothenyl-beta-aminoethyl)-disulfide] is a compound used clinically to decrease plasma triglycerides and to increase HDL cholesterol. To understand the mechanism of action of this drug, its effect on the synthesis of cholesterol in cultured skin fibroblasts was assessed. The addition of pantethine (100-200 microM) to cultured cells caused an 80% inhibition in cholesterol synthesis as measured by the incorporation of radiolabeled acetate or mevalonolactone. Inhibition occurred within 4 h of adding the drug and was specific for pantethine; other sulfur-containing compounds such as dithiothreitol, glutathione, coenzyme A and cystine did not inhibit. The inhibition of cholesterol synthesis resulted in the accumulation of radiolabeled methyl sterols. The drug also inhibited total fatty acid synthesis. The amount of [14C]pantethine detected in the cells is very low and represented less than 0.5% of the radiolabeled pantethine added in the medium. At low pantethine concentrations, the drug had negligible effects on the biosynthesis of DNA, protein and phospholipid. Topics: Acetates; Cholesterol; Depression, Chemical; DNA; Fatty Acids; Fibroblasts; Humans; Lanosterol; Mevalonic Acid; Pantetheine; Protein Biosynthesis; Skin; Sulfhydryl Compounds | 1982 |
Effects of some hypolipidemic drugs on biochemical values and on hepatic peroxisomal enzymes of normolipemic rat.
Effects of vitamin B2-butyrate, nicomol, ML-236B, KF 1492 and pantethine, which are hypolipidemic drugs, on biochemical values and on hepatic peroxisomal enzymes of normolipemic rat. 1) Vitamin B2-butyrate (100 mg/kg) and nicomol (lg/Kg) increased carnitine acetyltransferase and D-amino acid oxidase activities, respectively, while these drugs had no influence on body weight, liver weight, serum and liver triglyceride, and serum and liver cholesterol levels. 2) ML-236B (300 mg/kg) had no influence on biochemical values and on activities of peroxisomal enzymes containing catalase. 3) KF 1492 (300 mg/kg) had no influence on the biochemical values, but an increase in the activities of fatty acyl-CoA oxidizing system (FAOS) and carnitine acetyltransferase (CAT) participating hepatic lipid metabolism was observed. 4) Pantethine (lg/kg) had no influence on the biochemical values, except a little decrease in the growth rate. However, increase by about 10% in the activities of urate oxidase and D-amino acid oxidase was observed. Catalase activity was decreased to 60% of control level. From these results, it is concluded that, in contrast to clofibrate, vitamin B2-butyrate, nicomol, ML-236B, KF 1492 and pantethine have little influence on the lipid metabolism of normolipemic animal and on the hepatic peroxisomal enzymes, indicating that the action mechanism of these drugs may be different from that of clofibrate and that the participation of hepatic peroxisomes in hypolipidemic activities of these drugs may be little if any. Topics: Animals; Carnitine O-Acetyltransferase; Cyclohexanols; Hypolipidemic Agents; Liver; Lovastatin; Microbodies; Naphthalenes; Nicotinic Acids; Organoids; Pantetheine; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Inbred Strains; Riboflavin | 1981 |
Influence of pantethine on platelet volume, microviscosity, lipid composition and functions in diabetes mellitus with hyperlipidemia.
The in vivo effects of pantethine were investigated on serum lipids and platelet lipid and platelet functions in 31 diabetic patients with hyperlipidemia. Pantethine decreased cholesterol from 236 +/- 62 mg/dl (M +/- SD) to 217 +/- 51 mg/dl (p less than 0.01) and increased high density lipoprotein cholesterol from 40 +/- 11mg/dl to 43 +/- 15 mg/dl. The diabetic platelets were larger when accompanied by higher microviscosity that healthy platelets. The characteristics of lipid composition in diabetic platelets were high levels of free cholesterol, phospholipid, triglyceride, cholesterol ester, palmitoleic acid, linoleic acid and palmitoleic acid/palmitic acid and low levels of the molar ratio of free cholesterol/phospholipids, phosphatidylethanolamine, oleic acid, arachidonic acid and oleic acid/stearic acid. Pantethine normalized these values of fatty acids to the control levels, and concomitantly reduced significantly the hyperaggregation of platelets induced by 10(6) M ADP and the hyper-ADP release reaction from platelets when exposed to 2 microgram of collagen, and made the volume smaller and the microviscosity lower after oral administration. From these data, it was concluded that pantethine normalized the abnormalities of serum lipids as well as platelet lipid compositions and subsequently reduced the hyper-aggregation and hyper-release reactions through the changes of volume and microviscosity of the platelets in diabetes mellitus with hyperlipidemia. Topics: Blood Platelets; Blood Viscosity; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hyperglycemia; Lipids; Male; Pantetheine; Platelet Adhesiveness; Platelet Aggregation; Sulfhydryl Compounds | 1981 |
The effect of pantethine, a precursor of coenzyme A, on bile acids and lipids in rats fed with a cholesterol diet.
Topics: Animals; Bile Acids and Salts; Cholesterol, Dietary; Female; Lipid Metabolism; Lipids; Pantetheine; Rats; Rats, Inbred Strains; Sulfhydryl Compounds | 1981 |
[Effects of soysterol, pantethine and dl-alpha-tocopheryl nicotinate on hyperlipemia in rats (author's transl)].
Topics: Animals; Body Weight; Hyperlipidemias; Hypolipidemic Agents; Lipid Metabolism; Liver; Male; Nicotinic Acids; Organ Size; Pantetheine; Phytosterols; Rats; Rats, Inbred Strains; Sulfhydryl Compounds; Vitamin E | 1981 |
[Relationship between ADCC effector cells and the combination therapy of pantethine and lecithin--a proposal for management of patients with HBsAg carrier state (author's transl)].
Topics: Adult; Antibody-Dependent Cell Cytotoxicity; Carrier State; Drug Therapy, Combination; Female; Hepatitis B; Hepatitis B Surface Antigens; Humans; Male; Middle Aged; Pantetheine; Phosphatidylcholines; Sulfhydryl Compounds | 1981 |
Studies in search of modifiers of the toxicity of mercurials and speculations on its biochemical mechanism.
Topics: Animals; Coenzyme A; Cysteine; Glutathione; Goldfish; Mercury; Methylmercury Compounds; Pantetheine | 1981 |
[Effect of pantethine on the lipoprotein abnormalities in survivors of cerebral infarction (author's transl)].
Topics: Cerebral Infarction; Cholesterol; Humans; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Pantetheine; Sulfhydryl Compounds | 1980 |
[Study of enhancement of LCAT activity (author's transl)].
Topics: Adult; Arteriosclerosis; Drug Therapy, Combination; Humans; Kidney Diseases; Male; Pantetheine; Phosphatidylcholine-Sterol O-Acyltransferase; Phosphatidylcholines | 1980 |
[CLINICAL EFFECTS OF PANTETHINE ON NEUROLOGICAL DISORDERS].
Topics: Drug Therapy; Humans; Nervous System Diseases; Pantetheine; Pantothenic Acid; Pharmacology | 1965 |
[Histochemical aspects of the rat lung after treatment with prednisone and prednisone-pantethine].
Topics: Animals; Lung Diseases; Pantetheine; Pantothenic Acid; Prednisone; Rats | 1963 |
[Inhibition by pantethine of pulmonary hemorrhagic manifestations caused by prednisone. Experimental research in the rat].
Topics: Animals; Hemorrhage; Lung Diseases; Pantetheine; Pantothenic Acid; Prednisone; Rats | 1963 |
PANTETHINE-REQUIRING BACTEROIDES.
Reeves, Richard E. (Louisiana State University School of Medicine, New Orleans). Pantethine-requiring Bacteroides. J. Bacteriol. 85:1197-1201. 1963.-Growth of a culture of gram-negative streptobacilli, provisionally designated Bacteroides symbiosus, required a preformed source of pantetheine (pantethine or coenzyme A). Five types of organisms were isolated from the parent culture, and all exhibited a pantethine requirement. Pantothenate neither replaced nor spared the pantethine requirement of these organisms. Of the five isolated bacterial types, three were characterized by producing low, medium, and high optical densities, respectively, in a thiomalate medium. A fourth type was distinguished by cells which would not pack upon centrifugation, and a fifth by its high content of stored carbohydrate. Two of the five types seem well-suited to the growth of Entamoeba histolytica in the MS-F ameba-culture system. In addition to pantethine, these organisms required biotin, folic acid, pyridoxine, thiamine, and choline. A minimal defined medium was elaborated for one of the isolated bacterial types. B. symbiosus ATCC 12829 is proposed as a test organism for pantetheine in the presence of pantothenate. Topics: Bacteroides; Biotin; Choline; Coenzyme A; Culture Media; Entamoeba histolytica; Folic Acid; Pantetheine; Pyridoxine; Research; Spectrophotometry; Thiamine | 1963 |
[In vitro effect of pantethine on the secretion of 21-C-corticosteroids by the ox adrenal].
Topics: Adrenal Cortex Hormones; Glucocorticoids; In Vitro Techniques; Pantetheine; Pantothenic Acid; Pregnadienes | 1962 |
[Determination of pantethine in the presence of pantothenic acid].
Topics: Health Services; Pantetheine; Pantothenic Acid | 1961 |
Propionic acid metabolism. II. Enzymatic synthesis of lactyl pantethine.
Topics: Lactates; Pantetheine; Pantothenic Acid; Propionates; Pseudomonas | 1959 |
[The action of pantethine on the take of the homoplastic bone grafts].
Topics: Amines; Bone Transplantation; Humans; Pantetheine; Pantothenic Acid | 1959 |
[Lipotropic & liver protective effect of pantethine in experimental liver diseases induced by Handler diet & carbon tetrachloride].
Topics: Carbon Tetrachloride; Diet; Lipotropic Agents; Liver Diseases; Pantetheine; Pantothenic Acid; Sulfides | 1957 |
[Effect of pantethine on Co60 distribution].
Topics: Cobalt; Pantetheine; Pantothenic Acid; Sulfides | 1956 |
[Pantethine].
Topics: Pantetheine; Pantothenic Acid | 1955 |
[Initial clinical experiments with pantethine].
Topics: Humans; Pantetheine; Pantothenic Acid | 1955 |
Pantethine and casein hydrolyzate in the growth of certain lactobacilli.
Topics: Caseins; Humans; Lactobacillus; Pantetheine | 1955 |
Phosphorylation of pantothenic acid and pantethine by an enzyme from Proteus morganii.
Topics: Pantetheine; Pantothenic Acid; Phosphorylation; Proteus | 1955 |
[Effect of pantothenic acid, pantethine and phosphorylated pantethine on carotene formation in Mucor hiemalis].
Topics: Carotenoids; Fungi; Lipogenesis; Mucor; Pantetheine; Pantothenic Acid; Pigments, Biological | 1954 |
Pantethine and related forms of the Lactobacillus bulgaricus factor (LBF).
Topics: Lactobacillus; Pantetheine; Pantothenic Acid | 1953 |
The relationship of pantethine to naturally occurring forms of the Lactobacillus bulgaricus factor.
Topics: Lactobacillus; Pantetheine; Pantothenic Acid; Sulfhydryl Compounds | 1952 |
The comparative activities of pantethine, pantothenic acid, and coenzyme A for various microorganisms.
Topics: Coenzyme A; Humans; Pantetheine; Pantothenic Acid | 1951 |
I. Activity of LBF (pantethine) in acetylation of sulfanilamide by pigeon liver extract.
Topics: Acetylation; Animals; Columbidae; Liver; Liver Extracts; Pantetheine; Pantothenic Acid; Sulfanilamide; Sulfanilamides | 1951 |
PANTETHINE, pantothenic acid and the Lactobacillus bulgaricus factor.
Topics: Humans; Lactobacillus; Pantetheine; Pantothenic Acid | 1951 |