Hypolipidemic effect of pantothenic acid derivatives in mice with hypothalamic obesity induced by aurothioglucose.

Exp Toxicol Pathol 2001 Oct;53(5):393-8

Naruta E, Buko V.

Department of Experimental Hepathology, Institute of Biochemistry, National Academy of Sciences, Grodno, Belarus.

The hypolipidemic effects of pantothenic acid derivatives (phosphopantothenate, panthenol and pantethine) were studied in mice with hypothalamic obesity. Hypothalamic obesity in mice was induced by single injection of aurothioglucose (300 mg/kg body wt, i.p.). All the tested substances were administered during the last 10 days before decapitation (i.m., of dosage equivalent to 150 mg/kg body wt of phosphopantothenate). The studied substances inhibited the weight gain of the animals with hypothalamic obesity over the last 10 days of the experiment. The treatment with aurothioglucose increased food intake and mean body weight, blood glucose level; insulin, serum total cholesterol, triglyceride, the sum of LDL + VLDL and LDL-cholesterol concentration; triglyceride and cholesterol fractions in the liver; triglyceride and FFA content as well as lipoprotein lipase activity in adipose tissue of experimental mice. The administration of the assay compounds lowered food intake and mean body weight, insulin and glucose levels and decreased the content of triglycerides, total cholesterol and cholesterol esters in serum and adipose tissue as well as raised the activity of lipoprotein lipase in adipose tissue and serum lipolytic activity in obese mice. Among the compounds studied the reverse effect of panthenol was especially pronounced. The mechanism of hypolipidemic effects of pantothenic acid derivatives can be related to the reduced resistance to insulin and activation of lipolysis in serum and adipose tissue.

PMID: 11817109 [PubMed - indexed for MEDLINE]

The effects of pantethine on fatty liver and fat distribution.

J Atheroscler Thromb 2000;7(1):55-8

Osono Y, Hirose N, Nakajima K, Hata Y.

Health Administration Center, Aoyama Gakuin University, Tokyo, Japan.

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.

PMID: 11425046 [PubMed - indexed for MEDLINE]

Inhibition of acetyl-CoA carboxylase by cystamine may mediate the hypotriglyceridemic activity of pantethine.

Med Hypotheses 2001 Mar;56(3):314-7

McCarty MF.

Pantox Laboratories, San Diego, CA 92109, USA.

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. Copyright 2001 Harcourt Publishers Ltd.

PMID: 11359352 [PubMed - indexed for MEDLINE]

Nutritional and botanical interventions to assist with the adaptation to stress.

Altern Med Rev 1999 Aug;4(4):249-65

Kelly GS.

Prolonged stress, whether a result of mental/emotional upset or due to physical factors such as malnutrition, surgery, chemical exposure, excessive exercise, sleep deprivation, or a host of other environmental causes, results in predictable systemic effects. The systemic effects of stress include increased levels of stress hormones such as cortisol, a decline in certain aspects of immune system function such as natural killer cell cytotoxicity or secretory-IgA levels, and a disruption of gastrointestinal microflora balance. These systemic changes might be a substantial contributor to many of the stress-associated declines in health. Based on human and animal research, it appears a variety of nutritional and botanical substances - such as adaptogenic herbs, specific vitamins including ascorbic acid, vitamins B1 and B6, the coenzyme forms of vitamin B5 (pantethine) and B12 (methylcobalamin), the amino acid tyrosine, and other nutrients such as lipoic acid, phosphatidylserine, and plant sterol/sterolin combinations - may allow individuals to sustain an adaptive response and minimize some of the systemic effects of stress.

PMID: 10468649 [PubMed - indexed for MEDLINE]

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Pantethine inhibits the formation of high-Tc protein aggregates in gamma B crystallin solutions.

Curr Eye Res 1996 Dec;15(12):1182-90

Friberg G, Pande J, Ogun O, Benedek GB.

Department of Physics, Massachusetts Institute of Technology, Cambridge, USA.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

PMID: 9018433 [PubMed - indexed for MEDLINE]

Effects of antihyperlipidemic drugs and diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia.

Clin Ther 1996 May-Jun;18(3):477-82

Nomura H, Kimura Y, Okamoto O, Shiraishi G.

Department of Internal Medicine, Shinkokura Hospital, Kitakyushu, Japan.

We compared the efficacy of two antihyperlipidemic drugs and the efficacy of diet plus exercise therapy in the treatment of patients with moderate hypercholesterolemia. The study included 48 patients with moderate hypercholesterolemia (serum total cholesterol [TC], 250 to 320 mg/dL). Patients were divided into three groups: group A--patients administered 10 mg/d of pravastatin; group B--patients administered 500 mg/d of probucol and 600 mg/d of pantethine; and group C--patients administered diet plus exercise therapy. The serum TC and serum high-density lipoprotein cholesterol (HDL-C) values were determined via enzymatic methods before initiation of each therapy and after 4 and 8 weeks of therapy. An atherogenic index (AI) was also calculated. The results indicated that TC showed a statistically significant decrease in all three groups at 4 and 8 weeks (P < 0.001 and P < 0.05, respectively); the HDL-C value did not change significantly in groups A and C, but it had a statistically significant decrease in group B at 4 and 8 weeks. The AI showed a statistically significant decrease in group A at 4 and 8 weeks of treatment and group C at 8 weeks; there were no significant changes in AI in group B. It may be concluded that as an antihyperlipidemic agent, pravastatin is more useful than probucol and that appropriate exercise and strict dietary management for 8 weeks achieve an efficacy close to that achieved by drug therapy.

Treatment of hyperlipemia in diabetic patients on dialysis with a physiological substance.

Am J Nephrol 1991;11(1):32-6

Coronel F, Tornero F, Torrente J, Naranjo P, De Oleo P, Macia M, Barrientos A.

Nephrology Department, Hospital Universitario San Carlos, Madrid, Spain.

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.

PMID: 2048576 [PubMed - indexed for MEDLINE]

Pharmacologic and surgical treatment of dyslipidemic children and adolescents.

Ann N Y Acad Sci 1991;623:275-84

Hoeg JM.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.

A wide variety of treatment modalities have been used in children with dyslipidemias to reduce the concentrations of atherogenic lipoprotein particles. Most of the published experience has focused upon children with familial hypercholesterolemia (FH). A variety of pharmacologic regimens have been utilized with variable degrees of success. The bile acid sequestrants colestipol and cholestyramine, lovastatin, pantethine, paraminosalicylic acid, and fenofibrate have all been successful in reducing total blood cholesterol concentrations by 18-24% in hypercholesterolemic children. Of these medications, only the bile acid sequestrants are not absorbed into the circulation. This theoretic advantage is paralled by long-term safety studies which indicate the absence of serious adverse effects with bile acid sequestrant therapy. Therefore, the bile acid sequestrants represent the drugs of choice in treating severely dyslipidemic children. In selected cases of profoundly dyslipidemic children, other therapeutic strategies have been utilized. Most of these efforts have been directed in the treatment of the child homozygous for FH. Despite the lipid lowering effects of partial ileal bypass surgery in hypercholesterolemic adults, homozygous familial hypercholesterolemic children are not adequately treated by this approach. Portacaval shunt has reduced the total cholesterol concentrations by 20-35% in homozygous FH children without having a negative impact on growth and development. These children have, however, gone on to develop atherosclerotic cardiovascular disease despite therapy. Liver transplantation has led to virtual normalization of the plasma lipoprotein concentrations in 3 children homozygous for familial hypercholesterolemia, and there is evidence for regression of vascular lesions in the coronary arteries in one of these children. However, considering the expense, the difficulty in posttransplantation management, and the irreversible nature of the therapy, liver transplantation should be reserved as the therapy of last resort for homozygous FH. The best therapy for FH homozygotes is the frequent removal of the atherogenic lipoproteins by one of the several apheresis procedures currently available. Total plasma exchange, immunoadsorption, membrane filtration, dextran sulfate adsorption, and heparin extracorporeal precipitation have all been used successfully in significantly reducing the concentrations of total and low-density lipoprotein cholesterol. Studies currently under way will more extensively evaluate the long-term safety as well as the efficacy of apheresis procedures.

PMID: 2042836 [PubMed - indexed for MEDLINE]

Evaluation of the cholesterol-lowering effectiveness of pantethine in women in perimenopausal age.

Minerva Med 1990 Jun;81(6):475-9

Binaghi P, Cellina G, Lo Cicero G, Bruschi F, Porcaro E, Penotti M.

Servizio di Cardiologia, Istitut Clinici di Perfezionamento, Milano.

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.

PMID: 2359503 [PubMed - indexed for MEDLINE]

Therapeutic efficacy of pantothenic acid preparations in ischemic heart disease patients

Vopr Pitan 1987 Mar-Apr;(2):15-7

Borets VM, Lis MA, Pyrochkin VM, Kishkovich VP, Butkevich ND.

[Article in Russian]

The therapeutic effectiveness of the pantothenic acid drugs: calciipantothenas and pantethine, was studied in 182 patients with coronary heart disease and stable angina of effort. It is shown that both the drugs produce favourable effects on certain parameters of hemodynamics, on the metabolism of lipids, riboflavin and ascorbic acid. It is recommended that the administration of calciipantothenas in a dose of 300 mg/day, during 3 weeks, be included into the combined treatment of coronary patients with no manifest disorders of lipid metabolism. Patients with manifest hyperlipidemia should be administered pantethine in a dose of 500 mg/day.

PMID: 3590676 [PubMed - indexed for MEDLINE]

Effect of oral treatment with pantethine on platelet and plasma phospholipids in IIa hyperlipoproteinemia.

Angiology 1987 Mar;38(3):241-7

Prisco D, Rogasi PG, Matucci M, Paniccia R, Abbate R, Gensini GF, Neri Serneri GG.

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.

PMID: 3551695 [PubMed - indexed for MEDLINE]

Pantethine inhibits cholesterol and fatty acid syntheses and stimulates carbon dioxide formation in isolated rat hepatocytes.

J Lipid Res 1987 Feb;28(2):152-61

Cighetti G, Del Puppo M, Paroni R, Fiorica E, Galli Kienle M.

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.

PMID: 3106549 [PubMed - indexed for MEDLINE]

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Clinical use of pantethine by parenteral route in the treatment of hyperlipidemia

Acta Biomed Ateneo Parmense 1987;58(5-6):143-52

Arsenio L, Bodria P, Bossi S, Lateana M, Strata A.

[Article in Italian]

Servizio di Malattie del Ricambio e Diabetologia, Ospedali Riuniti, Parma.

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.

PMID: 2970754 [PubMed - indexed for MEDLINE]

Lipoprotein changes induced by pantethine in hyperlipoproteinemic patients: adults and children.

Int J Clin Pharmacol Ther Toxicol 1986 Nov;24(11):630-7

Bertolini S, Donati C, Elicio N, Daga A, Cuzzolaro S, Marcenaro A, Saturnino M, Balestreri R.

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.

PMID: 3098691 [PubMed - indexed for MEDLINE]

Effect of probucol, pantethine and their combinations on serum lipoprotein metabolism and on the incidence of atheromatous lesions in the rabbit.

Jpn J Pharmacol 1986 Jun;41(2):211-22

Tawara K, Ishihara M, Ogawa H, Tomikawa M.

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.

PMID: 3747267 [PubMed - indexed for MEDLINE]

Effects of pantethine on cholesterol synthesis from mevalonate in isolated rat hepatocytes.

Atherosclerosis 1986 Apr;60(1):67-77

Cighetti G, Del Puppo M, Paroni R, Galli G, Kienle MG.

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.

PMID: 3707674 [PubMed - indexed for MEDLINE]

Clin Nephrol 1986 Feb;25(2):70-4

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Pantethine improves the lipid abnormalities of chronic hemodialysis patients: results of a multicenter clinical trial.

Atherosclerosis 1986 Apr;60(1):67-77

Donati C, Barbi G, Cairo G, Prati GF, Degli Esposti E.

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.

PMID: 3516477 [PubMed - indexed for MEDLINE]

Effectiveness of long-term treatment with pantethine in patients with dyslipidemia.

Clin Ther 1986;8(5):537-45

Arsenio L, Bodria P, Magnati G, Strata A, Trovato R.

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.

PMID: 3094958 [PubMed - indexed for MEDLINE]

Effects of pantethine on in-vitro peroxidation of low density lipoproteins.

Atherosclerosis 1985 Oct;57(1):99-106

Bon GB, Cazzolato G, Zago S, Avogaro P.

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.

PMID: 4074466 [PubMed - indexed for MEDLINE]

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The effects of pantethine on lipid and lipoprotein abnormalities in survivors of cerebral infarction.

Artery 1985;12(4):234-43

Murai A, Miyahara T, Tanaka T, Sako Y, Nishimura N, Kameyama M.

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.

PMID: 3935096 [PubMed - indexed for MEDLINE]

Pantethine reduces plasma cholesterol and the severity of arterial lesions in experimental hypercholesterolemic rabbits.

Atherosclerosis 1984 Dec;53(3):255-64

Carrara P, Matturri L, Galbussera M, Lovati MR, Franceschini G, Sirtori CR.

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.

PMID: 6442152 [PubMed - indexed for MEDLINE]

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Controlled evaluation of pantethine, a natural hypolipidemic compound, in patients with different forms of hyperlipoproteinemia.

Atherosclerosis 1984 Jan;50(1):73-83

Gaddi A, Descovich GC, Noseda G, Fragiacomo C, Colombo L, Craveri A, Montanari G, Sirtori CR.

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.

PMID: 6365107 [PubMed - indexed for MEDLINE]

Hyperlipidemia, diabetes and atherosclerosis: efficacy of treatment with pantethine

Acta Biomed Ateneo Parmense 1984;55(1):25-42

Arsenio L, Caronna S, Lateana M, Magnati G, Strata A, Zammarchi G.

[Article in Italian]

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.

PMID: 6232801 [PubMed - indexed for MEDLINE]

Effect of pantethine on the biosynthesis of cholesterol in human skin fibroblasts.

Atherosclerosis 1982 Sep;44(3):261-73

Ranganathan S, Jackson RL, Harmony JA.

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.

PMID: 7150392 [PubMed - indexed for MEDLINE]

Effect of pantethine on cholesterol ester metabolism in rat arterial wall.

Atherosclerosis 1980 May;36(1):75-80

Shinomiya M, Matsuoka N, Shirai K, Morisaki N, Sasaki N, Murano S, Saito Y, Kumagai A.

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.

PMID: 7387778 [PubMed - indexed for MEDLINE]