thiobarbituric-acid and Disease-Models--Animal

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.

Topics: Administration, Oral; Animals; Antioxidants; CD4-Positive T-Lymphocytes; Disease Models, Animal; Female; Forkhead Transcription Factors; Glutathione; Interleukin-2 Receptor alpha Subunit; Interleukin-6; Lactobacillus; Lupus Erythematosus, Systemic; Mice; Mice, Inbred NZB; Probiotics; RNA, Messenger; Thiobarbiturates; Toll-Like Receptors; Tumor Necrosis Factor-alpha

Depression is frequently encountered during Parkinson's disease (PD) as a non-motor feature, which has been reported to cause and exaggerate motor deficits and neurodegenerative events in experimental PD models. We studied the effect of chronic mild stress (CMS) (pre, post and pre & post) exposure mediated depression on motor and non-motor symptoms, oxidative stress, inflammation and brain derived neurotrophic factor (BDNF) levels and its related signalling molecules against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced neurotoxicity in mice. CMS and MPTP/p-coexposed C57BL/6 mice exhibited low neuromuscular strength and stride length with enhanced oxidative stress and inflammation as compared to CMS or MPTP/p alone exposed mice. Coexposure diminished the levels of BDNF and expressions of p-TrkB, p-ERK/ERK, p-AKT/AKT and p-CREB in nigrostriatal regions as compared to those of the alone exposure. CMS alone exposed mice showed more anxiety related behaviour with diminished expression of serotonin transporter as compared to MPTP/p alone injected group. Post-stress exposure to MPTP/p mice exhibited lowest motor and reflecting higher anxiety state with greatest enhancement in inflammation and reduction in the protein expression of stress and cell signalling markers as compared to pre and pre & post stress exposed PD mice. However, pre- and pre & post CMS exposed PD animals are more vulnerable to oxidative stress as compared with post-stress experienced MPTP/p mice. CMS mediated depression exacerbates motor/non-motor symptoms in MPTP/p-PD animals by modulating oxidative stress and various signalling molecules. Our results suggested that stress induced NMS can accelerate neurodegenerative processes in the PD in a progressive or expedited manner.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Adjuvants, Pharmaceutic; Animals; Body Weight; Brain-Derived Neurotrophic Factor; Calcium-Binding Proteins; Catalase; Disease Models, Animal; Exploratory Behavior; Glial Fibrillary Acidic Protein; Male; Maze Learning; Mice; Mice, Inbred C57BL; Microfilament Proteins; Muscle Strength; Parkinsonian Disorders; Probenecid; Signal Transduction; Stress, Psychological; Superoxide Dismutase; Thiobarbiturates; Thiobarbituric Acid Reactive Substances

Hyperhomocysteinemia (HHC) has been reported to be one of risk factors for cardiovascular disease. We investigated the effects of HHC on blood pressure regulation and its association with damage to the thoracic aorta and imbalance of redox in plasma in rats. Rats were fed a methionine enriched diet (Met diet) or a methionine and cholesterol (Met+Chol diet) enriched diet for 16 weeks to create a subchronic HHC model, in which the plasma concentration of homocysteine was about 7 times higher than that of control rats. The increase in systolic blood pressure (Δ-SBP) from sympathetic stimulation by L-epinephrine was 2- to 3-fold larger in HHC model in rats than that in control rats after several weeks of the treatment. These findings suggest that HHC deteriorates vaso-regulatory function, which could bring on an increased risk of cardiovascular events in humans. In addition, some of the elastic lamellae in the aorta were disrupted in the HHC group. However, the content of cross-linkages which give elasticity and mechanical strength in the lamellae, was not significantly different between HHC and control rats. Also plasma concentrations of thiobarbituric acid reactive substance and glutathione as indicators for redox balance in plasma were not different. In conclusion, the deterioration of vaso-regulation in HHC model in rats might be caused by the damage to elastic lamellae in the aorta, and not by oxidative stresses.

Topics: Animals; Aorta, Thoracic; Blood Pressure; Cardiovascular Diseases; Disease Models, Animal; Elastic Tissue; Epinephrine; Homocysteine; Humans; Hyperhomocysteinemia; Male; Methionine; Oxidation-Reduction; Rats, Sprague-Dawley; Risk Factors; Thiobarbiturates

Metabolic syndrome is a growing worldwide health problem. We evaluated the effects of wine grape powder (WGP), rich in antioxidants and fiber, in a rat model of metabolic syndrome induced by a high fructose diet. We tested whether WGP supplementation may prevent glucose intolerance and decrease oxidative stress in rats fed with a high fructose diet.. Male Sprague-Dawley rats weighing 180 g were divided into four groups according to their feeding protocols. Rats were fed with control diet (C), control plus 20 % WGP (C + WGP), 50 % high fructose (HF) or 50 % fructose plus 20 % WGP (HF + WGP) for 16 weeks. Blood glucose, insulin and triglycerides, weight, and arterial blood pressure were measured. Homeostasis model assessment (HOMA) index was calculated using insulin and glucose values. A glucose tolerance test was performed 2 days before the end of the experiment. As an index of oxidative stress, thiobarbituric acid reactive substances (TBARS) level was measured in plasma and kidney, and superoxide dismutase was measured in the kidney.. Thiobarbituric acid reactive substances in plasma and renal tissue were significantly higher when compared to the control group. In addition, the area under the curve of the glucose tolerance test was higher in HF fed animals. Furthermore, fasting blood glucose, plasma insulin levels, and the HOMA index, were also increased. WGP supplementation prevented these alterations in rats fed with the HF diet. We did not find any significant difference in body weight or systolic blood pressure in any of the groups.. Our results show that WGP supplementation prevented hyperglycemia, insulin resistance and reduced oxidative stress in rats fed with HF diet. We propose that WGP may be used as a supplement in human food as well.

Topics: Animals; Antioxidants; Arterial Pressure; Blood Glucose; Disease Models, Animal; Fructose; Glucose Intolerance; Glucose Tolerance Test; Hyperglycemia; Insulin; Insulin Resistance; Kidney; Male; Metabolic Syndrome; Oxidative Stress; Phytotherapy; Powders; Rats, Sprague-Dawley; Superoxide Dismutase; Thiobarbiturates; Triglycerides; Vitis; Wine

The aim of the study was to examine the effects of chronic exercise training on seizures induced by homocysteine thiolactone (HCT) in adult rats. Rats were assigned to: sedentary control; exercise control; sedentary+HCT; exercise+HCT group. Animals in the exercise groups ran 30 min daily on a treadmill for 30 consecutive days (belt speed 20 m/min), while sedentary rats spent the same time on the treadmill (speed 0 m/min). On the 31st day, the HCT groups received HCT (8.0 mmol/kg), while the control groups received vehicle. Afterwards, convulsive behavior and EEG activity were registered. Lipid peroxidation, superoxide dismutase (SOD) and catalase (CAT) activity were ascertained in the rat hippocampus. No signs of seizures were registered in sedentary and exercise control rats. Seizure latency was increased, while number of seizure episodes and spike-and-wave discharges (SWD) in EEG were decreased in the exercise+HCT compared to the sedentary+HCT group. Seizure incidence, the severity thereof and duration of SWDs were not significantly different between these groups. Exercise partly prevented increase of lipid peroxidation and decrease of the SOD and CAT activity after HCT administration. These results indicate beneficial effects of exercise in model of HCT-induced seizures in rats, what could be, at least in part, a consequence of improved antioxidant enzymes activity.

Topics: Animals; Catalase; Disease Models, Animal; Electroencephalography; Hippocampus; Homocysteine; Male; Malondialdehyde; Oxidative Stress; Physical Conditioning, Animal; Rats, Wistar; Seizures; Superoxide Dismutase; Thiobarbiturates

Several lines of evidence suggest that the generation of reactive oxygen species (ROS) is of major importance in the pathogenesis of scleroderma, and thus antioxidant therapy may be useful for patients with an impaired oxidative defence mechanism.. To examine the effect of N-acetylcysteine (NAC) on skin fibrosis and oxidative stress in a bleomycin (BLM)-induced mouse model of scleroderma.. We used this mouse model to evaluate the effect of NAC on skin fibrosis and oxidative stress. Skin fibrosis was evaluated by histopathological examination and hydroxyproline content. To measure lipid peroxidation, we used a thiobarbituric acid-reactive species, malondialdehyde (MDA). Oxidative protein damage (carbonyl content) and the activities of catalase (CAT) and superoxide dismutase (SOD) were determined to evaluate oxidative stress in the skin tissue.. Treatment with NAC attenuated the skin fibrosis induced by BLM, significantly reducing the MDA and protein carbonyl content in these mice. SOD activity in BLM-only mice and BLM plus NAC-treated mice was increased compared with control mice. However, there was no significant difference in skin SOD activity of mice treated with both BLM and NAC compared with those treated with BLM only. In addition, CAT activity was not altered in the BLM plus NAC mice.. NAC treatment attenuates skin fibrosis in a BLM-induced mouse model of scleroderma, and this is associated with diminished oxidative stress. The results suggest that NAC may be a potential therapeutic agent for patients with scleroderma.

Topics: Acetylcysteine; Animals; Antibiotics, Antineoplastic; Bleomycin; Catalase; Disease Models, Animal; Female; Fibrosis; Free Radical Scavengers; Injections, Subcutaneous; Malondialdehyde; Mice; Mice, Inbred BALB C; Oxidative Stress; Reactive Oxygen Species; Scleroderma, Localized; Skin; Superoxide Dismutase; Thiobarbiturates

Recent studies have revealed that aberrant vitamin A signaling may lead to memory deficits in rodents. Present study investigates the potential of all-trans-retinoic acid (ATRA) an agonist at retinoid acid family of receptors, in cognitive dysfunctions associated with experimental dementia. Streptozotocin (STZ) [3 mg/kg, intracerebroventricularly (i.c.v)] was administered on alternate days (day 1 and day 3) to induce dementia in Swiss albino mice. STZ mice were administered ATRA (10 mg/kg; 20 mg/kg, p.o.) for a total of 19 days following second i.c.v injection of STZ [day 4 to day 22]. Morris water maze (MWM) test was performed on days 19, 20, 21, 22 and 23 to assess learning and memory of the animals. Following MWM test, the animals were sacrificed for biochemical and histopathological studies. Extent of oxidative stress was measured by estimating the levels of brain reduced glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity and serum cholesterol levels were also estimated. The brain level of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ produced a marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice showed marked accentuation of AChE activity, TBARS and MPO levels along with fall in GSH level. Further the stained micrographs of STZ-treated mice indicated pathological changes, severe neutrophilic infiltration and amyloid deposition. ATRA treatment significantly attenuated STZ-induced memory deficits, biochemical and histopathological alterations. The findings demonstrate that the memory restorative ability of ATRA may be attributed to its anti-cholinesterase, anti-oxidative and anti-inflammatory potential.

Topics: Alzheimer Disease; Animals; Brain; Dementia; Disease Models, Animal; Female; Glutathione; Male; Maze Learning; Memory Disorders; Mice; Peroxidase; Reactive Oxygen Species; Streptozocin; Thiobarbiturates; Tretinoin

Pyruvate, a potent endogenous antioxidant and an important metabolic fuel is essential for the cardiac function and tissue defense mechanism. The present study was evaluated to investigate whether pyruvate attenuates the development of cardiotoxicity in isoproterenol (ISO)-induced myocardial infarction by assessing hemodynamic, biochemical and histopathological parameters. Subcutaneous injection of ISO (85 mg/kg) administered for 2 days at an interval of 24h was used for induction of cardiotoxicity. ISO administration significantly decreased arterial pressure indices, heart rate, contractility {(+)LVdP/dt} and relaxation {(-)LVdP/dt} and increased left ventricular end-diastolic pressure. In addition, a significant reduction in activities of myocardial creatine phosphokinase-MB, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels along with increase in thiobarbituric acid reactive substances were also observed following ISO administration. However, pretreatment with pyruvate (0.25, 0.5 and 1.0 g/kg, p.o.) favorably modulated all most every studied parameters in ISO-induced myocardial injury. Furthermore, protective effect of pyruvate was confirmed by histopathological studies. Rats pretreated only with pyruvate did not produce significant change in hemodynamic, biochemical and histopathological parameters. Pyruvate at 0.50 and 1.0 g/kg doses was found to exert optimal cardioprotective effect against ISO-induced myocardial infarction. The results of our study suggest that pyruvate possessing antioxidant activity has a significant cardioprotective effect against ISO-induced myocardial injury.

Topics: Adrenergic beta-Agonists; Animals; Cardiotonic Agents; Disease Models, Animal; Heart; Hemodynamics; Injections, Subcutaneous; Isoproterenol; Male; Myocardial Infarction; Myocardium; Oxidative Stress; Oxidoreductases; Pyruvic Acid; Rats; Rats, Wistar; Thiobarbiturates

Oxidative stress and inflammation are constant features and major mediators of progression and cardiovascular complications of chronic kidney disease (CKD). Hydrogen sulfide (H(2)S) is an endogenous signaling gas, which possesses potent anti-oxidant, anti-inflammatory, anti-hypertensive and other regulatory functions. H(2)S is produced by cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulphurtransferase (MST). Plasma H(2)S is reduced in humans with hypertension, atherosclerosis and end-stage renal disease (ESRD). Atherosclerosis, hypertension and ischemia/reperfusion-induced acute kidney injury are associated with and, in part, mediated by diminished tissue H(2)S in experimental animals. Expression of the H(2)S-producing enzymes is reduced in the circulating leukocytes of patients with ESRD. However, the effect of CKD on expression of H(2)S-producing enzymes in the diseased kidney and other tissues is unknown and was studied here.. Subgroups of rats were subjected to 5/6 nephrectomy or sham operation and observed for 6-12 weeks. Expression of H(2)S-producing enzymes and H(2)S-producing capacity was measured in kidney, liver and brain tissues.. The CKD group exhibited oxidative stress and significant reduction of plasma H(2)S concentration. This was associated with marked reduction of H(2)S-producing capacity of the kidney and liver, marked downregulation of CBS, CSE and MST in the kidney and of CBS and CSE expression in the liver. However, expression of H(2)S-producing enzymes in the brain was not significantly altered in CKD rats.. CKD is associated with significant reduction in plasma H(2)S concentration, diminished remnant kidney and liver tissue H(2)S-producing capacity and downregulation of the H(2)S-producing enzymes. Given the potent anti-oxidant, anti-inflammatory and cytoprotective properties of H(2)S, its deficiency may contribute to progression of CKD and the associated complications.

Topics: Animals; Biomarkers; Blood Pressure Determination; Blotting, Western; Brain; Disease Models, Animal; Disease Progression; Down-Regulation; Hydrogen Sulfide; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Liver; Male; Malondialdehyde; Nephrectomy; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reference Values; Sensitivity and Specificity; Thiobarbiturates

Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adiponectin; Animals; Barbiturates; Cell Differentiation; Disease Models, Animal; Fatty Liver; Leptin; Male; Mice; Molecular Structure; Non-alcoholic Fatty Liver Disease; Rats; Rats, Wistar; Stereoisomerism; Structure-Activity Relationship; Thiobarbiturates

The effects of Cu(II) supplementation on glycemic parameters, advanced glycation end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic rats. The study was carried out on Wistar albino rats grouped as control (n = 10), CuCl(2) treated (n = 9), STZ (n = 10) and STZ,CuCl(2) treated (n = 9). STZ was administered intraperitoneally at a single dose of 65 mg/kg and CuCl(2), 4 mg copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period, glucose(mg/dl), Cu(microg/dl), TBARS(micromol/l), TAOC(mmol/l) were measured in plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood. Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric and spectrophotometric detectors connected on-line. Data were analyzed by the non-parametric Kruskal-Wallis and Mann-Whitney U test. In the STZ group glucose, GHb and AGE-peptide levels were all significantly higher than the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). CuCl(2) treated group had significantly lower glucose but significantly higher GHb, TAOC and TBARS levels than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001, respectively). STZ,CuCl(2) treated group had significantly higher GHb, TAOC and TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05, respectively); but only TAOC level was significantly higher than the STZ group (P < 0.01). This experimental study provides evidence that copper intake increases total antioxidant capacity in both nondiabetic and diabetic states. However despite the potentiated antioxidant defence, lipid peroxidation and glycation enhancing effects of CuCl(2) are evident under nondiabetic conditions.

Topics: Animals; Antioxidants; Copper; Diabetes Mellitus, Experimental; Dietary Supplements; Disease Models, Animal; Glutathione; Glycation End Products, Advanced; Lipid Peroxidation; Male; Rats; Rats, Wistar; Streptozocin; Thiobarbiturates

Validate the popular use of Plectranthus grandis in gastric disorders through the active components.. Isolation of barbatusin (BB) and 3beta-hydroxy-3-deoxibarbatusin (BBOH), diterpenes from Plectranthus grandis, and evaluation of their gastroprotective effect and possible mechanisms of action.. Isolation and chemical characterization of diterpenes from Plectranthus grandis by chromatographic and spectroscopic methods and evaluation of gastroprotective action of the diterpenes through ethanol-induced gastric injury in mice model. It was evaluated the effect of capsazepine, indomethacin and the role of nitric oxide and K(ATP-) channels on the gastroprotective effect of BBOH and BB. Additionally it was measured the concentrations of gastric mucus, non-proteic-sulfhydryl groups and total thiobarbituric acid-reactive substances.. Orally administered BBOH and BB at doses of 5 and 10mg/kg, markedly reduced the gastric lesions by 59 and 96%, and 32 and 76%, respectively, with superior results as compared to N-acetylcysteine (150 mg/kg, i.p.), reference compound that caused 85% lesion suppression. Although BBOH presented a higher gastroprotection than BB they act by similar mechanisms in relation to N-acetylcysteine, and prevent the depletion of gastric mucus, gastric mucosal non-proteic-sulfhydryl groups as well as the increase in thiobarbituric acid-reactive species. Moreover, the gastroprotective effect of BB was effectively blocked in mice pretreated with TRPV1 antagonist capsazepine, by the non-selective cyclooxygenase inhibitor indomethacin, or by the nitric oxide synthase inhibitor L-NAME but not by K(+)(ATP) channel inhibitor glibenclamide. In contrast, the gastroprotective effect of BBOH was blocked only by indomethacin and glibenclamide pretreatments.. The protective role for BBOH and BB affording gastroprotection against gastric damage induced by ethanol indicates that these compounds contribute for the activity of Plectranthus species. The different modes of action are probably related to differences in their chemical structure.

Topics: Acetylcysteine; Animals; Anti-Ulcer Agents; Antioxidants; Capsaicin; Disease Models, Animal; Diterpenes; Ethanol; Gastric Mucosa; Glyburide; Indomethacin; Male; Mice; Mucus; NG-Nitroarginine Methyl Ester; Phytotherapy; Plant Extracts; Plant Leaves; Plectranthus; Quinones; Stomach; Stomach Ulcer; Sulfhydryl Compounds; Thiobarbiturates

Diabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED.. To evaluate the effects of the antioxidant, AC3056 (2,6-di-t-butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED.. Erectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively.. The influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-kappaB (NF-kappaB) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined.. Eight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-kappaB expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 microM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 microM) was corrected by AC3056 (30 microM).. These results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes.

Topics: Animals; Antioxidants; Blotting, Western; Diabetes Mellitus; Disease Models, Animal; Drug Administration Schedule; Erectile Dysfunction; Humans; Lipid Peroxidation; Male; Nitric Oxide; Organosilicon Compounds; Penis; Rats; Rats, Sprague-Dawley; Thiobarbiturates

It has been proposed that reactive oxygen species play a causative role of gastric mucosal damage induced by increased gastric secretion. Gastrin-releasing peptide is a typical neuropeptide that stimulates acid secretion by release of gastrin. In the present work we have investigated the mechanism of indomethacin (IDM)-induced gastric ulcer caused by ROS and determined the effects of a selective gastrin-releasing peptide receptor antagonist, RC-3095, alone and in association with omeprazole (OM) and compared it with an established antioxidant compound N-acetyl cysteine (NAC). Adult male Wistar rats were pre-treated for 7 days with OM, RC-3095, NAC, both drugs and water (control). The animals were then submitted to fasting for 24h; IDM was administered. Rats were killed 6h after that and the stomachs were used for evaluation of macroscopic damage and oxidative stress parameters. Our results showed that IDM increased mitochondrial superoxide production; OM and RC-3095 alone did not prevent such effect, but the combination of these drugs was effective. TBARS assay revealed that IDM-induced lipid peroxidation in gastric tissue and that OM and RC-3095, alone or in combination, prevented this effect with superior action that NAC. Finally, we verified that IDM increased protein carbonyl content and that this effect was prevented RC-3095, alone or in combination with OM, being similar to standard antioxidant. The present results support the view that, besides the inhibition of acid secretion, the protective effects exerted by OM and RC-3095 against IDM-induced gastric damage can be ascribed to a reduction of gastric oxidative injury.

Topics: Animals; Bombesin; Disease Models, Animal; Gastric Mucosa; Gastritis; Indomethacin; Lipid Peroxidation; Male; Mitochondria; Omeprazole; Peptide Fragments; Protein Carbonylation; Proton Pump Inhibitors; Rats; Rats, Wistar; Receptors, Bombesin; Superoxides; Thiobarbiturates

Oxidative stress is considered to be a significant risk factor in the pathogenesis of many eye diseases associated with aging. The purpose of this study was to investigate the susceptibility of retinal tissue to reactive oxygen species (ROS)-induced damage, and to examine if this can be prevented by compounds having the ability to scavenge ROS as well as support the tissue bioenergetically via normal as well as anaplerotic metabolic pathways.. Experiments were conducted on retinas isolated from CD-1 mice. The isolated retinas were incubated in Medium 199, generating ROS by the action of xanthine oxidase and uricase on xanthine. Parallel experiments were conducted in the presence of pyruvate (10 mM). The extent of oxidative damage to the tissue was assessed by determining the levels of glutathione. Malonaldehyde was used as an index of the peroxidative degradation of lipids.. Exposure of the tissue to ROS resulted in a significant decrease in its glutathione content. There was a simultaneous increase in the level of malonaldehyde. These effects were substantially attenuated by pyruvate.. While ROS has been previously implicated in the genesis of many aging diseases of the retina, methods to prevent or treat them are currently in their infancy. The present investigations suggest that this can be accomplished by the use of certain compounds of endogenous origin, such as pyruvate, which have the dual properties of acting as ROS scavengers while also acting as metabolic agonists. By virtue of its oxyradical scavenging property, it is expected to inhibit the oxidative degradation of polyunsaturated fatty acids required to maintain the structural and functional integrity of the tissue.

Topics: Animals; Biomarkers; Disease Models, Animal; Malondialdehyde; Mice; Oxidative Stress; Pyruvic Acid; Reactive Oxygen Species; Retina; Retinal Diseases; Spectrophotometry; Thiobarbiturates; Treatment Outcome

The reactions of 1, 2-dihydro-2-thioxo-4, 6(1H, 5H)pyrimidinedione (1) with some pi-deficients have led to the formation of unexpected heterocyclic products such as anilinomethylenethioxopyrimidinedione, 2, 2'-bis(pyrimidinecarbothioamide), allylthioxopyrimidinecarbothioamide, indenopyranopyrimidine and benzofuropyrimidine derivatives. A possible mechanism for the formation of these products is discussed, and the biological activity is determined.

Topics: Animals; Cell Survival; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Heterocyclic Compounds; Humans; Hypnotics and Sedatives; In Vitro Techniques; Male; Mice; Pyrimidines; Thiobarbiturates; Thiones; Tumor Cells, Cultured

The adaptogenic and antioxidant properties of new Ukrainian plant drug "Poliphytolum" was investigated on the model of stress, which was caused of hypergravitation 2 and 5 N.m2/kg2 action. It was established that hypergravitation makes typical stressory disturbances in oxidative homeostasis. The normalization action of "Polyphytolum" on lipid peroxidation is more strong in liver, spleen and blood, and less more--in brain. It may be caused of low level the drug in the brain tissue.

Topics: Animals; Brain; Catalase; Disease Models, Animal; Hypergravity; Lipid Peroxidation; Male; Oxidative Stress; Phytotherapy; Plant Preparations; Plants, Medicinal; Rats; Spleen; Stress, Physiological; Superoxide Dismutase; Thiobarbiturates; Ukraine

Although age is a strong risk factor for atherosclerosis, it is unclear whether age may directly influence the process of atherogenesis. We, therefore, performed several studies in young (2-4 months old), mature (10-14 months old), and old (20-22 months old) mice to determine if the rate of aortic lesion formation increases with age, and whether this is related to increases in oxidative stress or vascular cell adhesion molecule (VCAM-1) expression in the aortic wall. In chow-fed low-density lipoprotein receptor-deficient (LDLR-/-) mice, plasma total cholesterol levels increased with age (250 +/- 52 mg/dl in young, 276 +/- 58 in mature, and 314 +/- 101 mg/dl in old mice). In contrast, the extent of atherosclerosis rose more rapidly, increasing from 3.6 +/- 2.7% of the aortic surface in mature mice to 18.2 +/- 8% in old mice. Plasma and tissue levels of antioxidant enzymes and molecules, as well as plasma thiobarbituric acid reactive substances and low-density lipoprotein susceptibility to oxidation, did not change with age. In a second study, VCAM-1 expression in the aortic arch and the extent of atherosclerosis in the aortic origin were significantly greater in old LDLR-/- mice than in young LDLR-/- mice. Additionally, after 1 month of a high-fat diet, which induced equally elevated plasma cholesterol levels in both young and old LDLR-/- mice, VCAM-1 expression and aortic lesion formation were still greater in old mice. The extent of atherosclerosis correlated well (r = .65,p <.01) with the expression of VCAM-1 in the aortic origin. In a final study, we measured VCAM-1 expression and atherosclerosis in young, mature, and old C57BL/6 mice, which have low plasma cholesterol levels (< or =100 mg/dl) when fed a standard chow diet. Although plasma cholesterol levels did not increase with age, old C57BL/6 mice had significantly more VCAM-1 expression in the aortic arch than did young mice. However, no lesions were observed in the aortic origin in either group. These data demonstrate that plasma cholesterol levels and VCAM-1 expression increase with age and suggest that this may contribute to the increased rate of atherosclerotic lesion formation in LDLR-/- mice. Importantly, the age-dependent increase in VCAM-1 expression does not appear to be related to plasma cholesterol levels. This study also suggests that in the absence of elevated plasma cholesterol, an increased expression of VCAM-1 alone is not sufficient for lesion formation.

Topics: Aging; Analysis of Variance; Animals; Aorta; Aortic Diseases; Arteriosclerosis; Catalase; Cholesterol; Dietary Fats; Disease Models, Animal; Gene Expression Regulation; Glutathione Peroxidase; Lipoproteins, LDL; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Oxidation-Reduction; Oxidative Stress; Receptors, LDL; Risk Factors; Superoxide Dismutase; Thiobarbiturates; Vascular Cell Adhesion Molecule-1

Lipid peroxidation was studied in the brain of Mongolian gerbils under conditions of complete ischemia followed by recirculation in the left hemisphere without recirculation in the right hemisphere. Thiobarbituric acid reactive products and the intensity of Fe2+-induced chemiluminescence were determined. The content of lipid peroxidation products in the brain tissue was increased not only under conditions of recirculation, but also at the ischemia stage during the limited access of oxygen. Thus, the destructive effect of free radicals may occur even during the early stage of ischemic injury of the brain.

Topics: Animals; Antioxidants; Brain; Brain Ischemia; Butylated Hydroxytoluene; Disease Models, Animal; Female; Gerbillinae; Lipid Peroxidation; Luminescent Measurements; Male; Reperfusion; Thiobarbiturates

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury.

Topics: Acute Kidney Injury; Animals; Antioxidants; Disease Models, Animal; Glomerular Filtration Rate; Kidney; Lipid Peroxidation; Male; Metallothionein; Rats; Rats, Wistar; Reactive Oxygen Species; Renal Circulation; Reperfusion Injury; Thiobarbiturates; Treatment Outcome; Zinc

Topics: Aldehydes; Animals; Disease Models, Animal; Dogs; Free Radicals; Hydrogen Peroxide; Hypoxanthine; Hypoxanthines; Lactates; Lactic Acid; Lipid Peroxidation; Malondialdehyde; Shock, Traumatic; Spectrometry, Fluorescence; Superoxides; Thiobarbiturates

The effect of SOD on staphylococcal arthritis has not been successfully evaluated to date. We developed an animal model to investigate the correlation. Using 16 rabbits divided into four groups, we injected two groups with staphylococcus aureus and the other two with NaCl. One group in each was also injected with SOD. The presence of SOD activity in untreated and infected knee joints of rabbits over a period of 72 hours showed no significant difference. TBA-reactive substances (TBARS) measured in joint fluid and plasma did differ in each of the groups, with the highest values found in animals with septic arthritis treated with SOD. This finding corresponded especially with the histological investigation. Joints of infected animals intra-articularly injected with SOD also showed histologically significantly more inflammation, a higher amount of bacteria in the joint cavity, and more distinct joint damage than joints injected only with bacteria. The mechanisms responsible for this SOD effect remain to be determined.

Topics: Animals; Arthritis, Infectious; Disease Models, Animal; Free Radicals; Hindlimb; Injections, Intra-Articular; Rabbits; Staphylococcal Infections; Superoxide Dismutase; Synovial Fluid; Thiobarbiturates

The rheumatoid synovium is capable of producing large amounts of IgG which may become modified by the actions of free radicals. A rat model of synovitis was established and challenged with both normal and free radical altered IgG. IgG was prepared from homologous pooled serum by high performance liquid chromatography, and free radical damage was induced by 15 minutes ultraviolet (UV) irradiation. The results showed a worsening in gross assessments of inflammation, increases in biochemical indices of lipid peroxidation, and also a rise in the proportion of IgG which, on reisolation, showed the characteristic fluorescence associated with free radical damage. This demonstrated how the presence of free radical altered IgG might convert an inflammatory insult to a more persistent stimulus, and the capacity of an environment subjected to continuing antigenic stimulation to induce further free radical damage to IgG.

Topics: Animals; Disease Models, Animal; Exudates and Transudates; Free Radicals; Immunoglobulin G; Immunohistochemistry; Iron; Leukocyte Count; Lipid Metabolism; Male; Rats; Rats, Inbred Strains; Synovitis; Thiobarbiturates