pantetheine and Body-Weight

In the course of a post-marketing surveillance program on the effectiveness and tolerability of pantethine in the treatment of hyperlipidemia, the effects of the drug were explored in 31 patients with dyslipidemia undergoing chronic hemodialysis. The mean duration of treatment was 9 months (min. 7 months, max. 24 months), with oral doses of 600 to 1200 mg of pantethine daily (mean daily dosage 970 mg). Improvement was noted in terms of total blood cholesterol in the 7 patients with basal hypercholesterolemia (p less than 0.01) and highly significant reduction of serum triglycerides. No variations of HDL-cholesterol or total Apo-A were detected. None of the patients experienced any adverse effects from the treatment. In the light of extensive experience with the drug, plus the results of this study, the authors conclude by stressing the importance of an effective and readily tolerated product, such as pantethine, for the treatment of dyslipidemia in patients on chronic hemodialysis.

Topics: Adult; Aged; Body Weight; Cholesterol; Clinical Trials as Topic; Female; Humans; Hyperlipidemias; Kidney Diseases; Male; Middle Aged; Pantetheine; Renal Dialysis; Sulfhydryl Compounds; Triglycerides

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

The pharmacological and antitumor effects of FR901537, a new aromatase inhibitor, isolated from Bacillus sp. No. 3072, were studied. Treatment for four consecutive days with FR901537 inhibited the androstenedione-induced increase in the uterus weight in immature rats. FR901537 had no effect on the uterus, adrenal glands, ovary or pituitary weights in mature rats following 14 days of treatment. The antitumor activity of FR901537 on 7,12-dimethylbenz(a)anthracene-induced mammary tumors was studied in ovariectomized, testosterone propionate (TP)-treated rats as a postmenopausal tumor model. Ovariectomy caused the regression of the mammary tumors and the growth of tumors was remarkably stimulated following TP treatment. Further, in the rats treated with FR901537 and TP, the TP-induced tumor growth was significantly inhibited by FR901537. These results suggest that FR901537 is a promising drug in the treatment of estrogen-dependent mammary tumors in postmenopausal women.

Topics: Aminoglutethimide; Animals; Antibiotics, Antineoplastic; Aromatase Inhibitors; Bacillus; Body Weight; Female; Mammary Neoplasms, Experimental; Molecular Structure; Organ Size; Pantetheine; Rats; Rats, Sprague-Dawley

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

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

Weanling rats were fed a pantothenic acid (PA)-free diet for 11 days. Although the animals did not show symptoms of vitamin deficiency, the concentrations of total and free CoA (analyzed with 2-oxoglutarate dehydrogenase), the levels of CoA, dephospho-CoA and 4'-phosphopantetheine (assayed together in the N-acetylation reaction) were decreased. As PA deficiency developed (by days 33-44 of the experiment), the reduction of the content of these metabolites and short-chain acyl-CoA became more pronounced. The level of long-chain acyl-CoA, the ratios of free CoA/total CoA and long-chain acyl-CoA/total CoA remained unchanged. The coenzyme biosynthetic precursors demonstrated the most marked response to the severity of PA deficiency. The relative stability of the hepatocyte CoA pool is interpreted in terms of the cytosol ability to deposit the vitamin in the form of pantothenate-protein complexes.

Topics: Acyl Coenzyme A; Animals; Body Weight; Coenzyme A; Liver; Male; Pantetheine; Pantothenic Acid; Proteins; 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

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

The total serum cholesterol level in rats fed on a high cholesterol diet (HCD) for 16 weeks was markedly higher than that in rats fed on a normal diet (ND), but pantethine reduced the increased level in rats fed on HCD (P less than 0.05). Acid cholesterol esterase activity (acid CEase) of arterial wall homogenates from rats fed on HCD was significantly lower than that of rats fed on ND (P less than 0.005). Acid CEase activity in the arterial wall of rats fed on HCD for 8 weeks and then ND for 8 weeks was less than that of rats fed on ND for 16 weeks. Acid CEase activity in the arterial wall was increased in rats fed on pantethine-containing diet. The ratio of cholesterol ester synthesizing activity to neutral cholesterol esterase (neutral CEase) activity was higher in rats fed on NCD than in those fed on ND. The ratio was lower in rats on the pantethine-containing diet than in those on NCD. The relationship between hypercholesterolemia and lipid metabolism in the arterial wall and effects of pantethine are discussed on the basis of these results.

Topics: Alanine Transaminase; Animals; Aorta; Body Weight; Cholesterol; Cholesterol Esters; Liver; Male; Organ Size; Pantetheine; Phospholipids; Rats; Sterol Esterase; Triglycerides