1. Effects of ethanol and pantothenic acid on brain acetylcholine synthesis.
Rivera-Calimlim L, Hartley D, Osterhout D. Department of Pharmacology, University of Rochester, School of Medicine and Dentistry, NY 14642.
Br J Pharmacol. 1988 Sep;95(1):77-82.
Measurements of brain acetylcholine (ACh) synthesis from precursor [14C]-pyruvate, pantothenic acid (PA) concentration in the brain, and blood ethanol (EtOH) concentration were made in rats treated with either ethanol (5-6 g kg-1 body wt daily) alone or ethanol with PA supplementation (100-200 mg kg-1 body wt daily). EtOH with or without PA was administered orally by either Lieber-Decarli liquid diet for 4 weeks and 4 months or by oral intubation for 1 and 4 days. Matched controls were given either ethanol-free liquid diet or saline. 2. ACh synthesis in the brain of rats treated with ethanol alone for 4 months was significantly (P less than 0.01) inhibited. PA concentration of the brain was diminished to 7.0% of the control value. 3. PA concentration in the brain of rats treated with ethanol plus PA for 4 months was three times that of rats treated with ethanol alone. ACh synthesis in rats with ethanol and PA supplementation was also significantly (P less than 0.01) higher. 4. There was no difference in blood EtOH concentration between rats treated with ethanol with or without PA supplement. 5. The EtOH effect on ACh synthesis and PA concentration in the brain was observed in the chronic treatments but not in the acute treatments. 6. Data suggest that chronic ethanol exposure may decrease ACh synthesis by depleting PA, a precursor for the synthesis of acetyl CoA. Acetyl CoA is an essential substrate for ACh synthesis.
Transport and metabolism
2. Pantothenic acid transport and metabolism in the central nervous system.
Am J Physiol. 1986 Feb;250(2 Pt 2):R292-7.
The mechanisms by which pantothenic acid (PA) enters and leaves brain, choroid plexus, and cerebrospinal fluid (CSF) were investigated by injecting [3H]PA either intravenously or intraventricularly into adult rabbits. [3H]PA, either alone or together with unlabeled PA, was infused at a constant rate into conscious rabbits. At 180 min, [3H]PA readily entered CSF, choroid plexus, and brain. In brain, CSF, and plasma, greater than 90% of the 3H was associated with [3H]PA. The addition of 200 mumol/kg PA to the infusion syringe decreased the penetration of [3H]PA into brain and CSF by approximately 70%. Two hours after the intraventricular injection of [3H]PA, [3H]PA was rapidly cleared from the CSF by a probenecid-sensitive mechanism. No metabolism of the [3H]PA occurred in brain. However, 18 h after the intraventricular injection of 37 microCi (34 nmol) of [3H]PA, approximately 40% of the 3H remaining in forebrain was converted to [3H]CoA. These results show that PA enters and leaves CSF and brain by saturable transport systems. However, [3H]PA is very slowly converted to [3H]CoA in brain in vivo.
Vitamins and lipid metabolism.
3. Fidanza A, Audisio M.
Acta Vitaminol Enzymol. 1982;4(1-2):105-14.
Vitamins play an essential role in lipid metabolism reactions and their presence is therefore absolutely necessary for these reaction to occur. The effect of pantothenic acid, niacin and riboflavin is here described. By transformation into coenzymes these vitamins are involved in fatty acid synthesis and oxidation reactions. Other vitamins, like vitamin B12, folic acid, vitamin C, and essential fatty acids influence lipid metabolism by different mechanisms. Coenzyme B12 and folate coenzyme provide to balance, by methionine synthesis, the pool of methyl radicals necessary for phospholipid biosynthesis. By its involvement in the microsomal respiratory chain, vitamin C promotes cholesterol transformation into bile acids. The essential fatty acids, mainly linoleic acid, are directly connected with cholesterol transport and plasma cholesterol decrease. It is suggested that many lipid metabolism disorders may be due to primary and secondary hypovitaminosis. Nicotinic acid and its derivatives have a particular pharmacological effect since they cause a HDL increase with LDL decrease and improve cholesterol transfer from LDL to HDL. Results of several experiments on the influence of pantothenic acid on polyunsaturated fatty acid metabolism are eventually reported, and these data are related to the effect of the administration of vitamin C at high doses on total cholesterol, triglyceride, lipoprotein, vitamin C and fatty acids of the different plasma lipid fractions.
4. Pantothenic acid protects jurkat cells against ultraviolet light-induced apoptosis.
Slyshenkov VS, Piwocka K, Sikora E, Wojtczak L. Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Free Radic Biol Med. 2001 Jun 1;30(11):1303-10.
Human leukemic T lymphocytes (Jurkat cells) were induced to undergo apoptosis by brief irradiation with ultraviolet C light (254 nm). This was accompanied by accumulation of lipid peroxidation products in the form of conjugated dienes, a decrease of total glutathione content, and a shift of its redox state towards the oxidized form. Preincubation of the cells with 1 mM pantothenate resulted in a significant elevation of total glutathione content of the cells, reaching its maximum level, 160% of the control, after 3 h. Similar increase was observed after preincubation with 5 mM N-acetylcysteine, a known precursor of glutathione. Both pantothenic acid and N-acetylcysteine alleviated the ultraviolet-induced decrease of glutathione content, diminished lipid peroxidation, and partly protected the cells against apoptosis produced by ultraviolet irradiation.
5. Mitochondrial, but not peroxisomal, beta-oxidation of fatty acids is conserved in coenzyme A-deficient rat liver.
Youssef JA, Song WO, Badr MZ. Division of Pharmacology, University of Missouri-Kansas City 64108, USA.
Mol Cell Biochem. 1997 Oct;175(1-2):37-42.
Hepatic coenzyme A (CoA) plays an important role in cellular lipid metabolism. Because mitochondria and peroxisomes represent the two major subcellular sites of lipid metabolism, the present study was designed to investigate the specific impact of hepatic CoA deficiency on peroxisomal as well as mitochondrial beta-oxidation of fatty acids. CoA deficiency (47% decrease in free CoA and 23% decrease in total CoA) was produced by maintaining weanling male Sprague-Dawley rats on a semipurified diet deficient in pantothenic acid (the precursor of CoA) for 5 weeks. Hepatic mitochondrial fatty acid oxidation of short-chain and long-chain fatty acids were not significantly different between control and CoA-deficient rats. Conversely, peroxisomal beta-oxidation was significantly diminished (38% inhibition) in livers of CoA-deficient rats compared to control animals. Peroxisomal beta-oxidation was restored to normal levels when hepatic CoA was replenished. It is postulated that since the role of hepatic mitochondrial beta-oxidation is energy production while peroxisomal beta-oxidation acts mainly as a detoxification system, the mitochondrial pathway of beta-oxidation is spared at the expense of the peroxisomal pathway when liver CoA plummets. The present study may offer an animal model to investigate mechanisms involved in peroxisomal diseases.
6. Amelioration of adverse effects of valproic acid on ketogenesis and liver coenzyme A metabolism by cotreatment with pantothenate and carnitine in developing mice: possible clinical significance.
Thurston JH, Hauhart RE. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110.
Pediatr Res. 1992 Apr;31(4 Pt 1):419-23.
Very young children with organic brain damage, intractable seizures, and developmental retardation are at particular risk of developing fatal hepatic dysfunction coincident with valproate therapy, especially if the children are also receiving other anticonvulsant drugs. The mechanism of valproate-associated hepatic failure in these children is unclear. There are two major theories of etiology. The first concerns the manyfold consequences of depletion of CoA due to sequestration into poorly metabolized valproyl CoA and valproyl CoA metabolites. The other theory proposes that the unsaturated valproate derivative 2-n-propyl-4-pentenoic acid and/or metabolically activated intermediates are toxic and directly cause irreversible inhibition of enzymes of beta-oxidation. The present study shows for the first time that in developing mice, when panthothenic acid and carnitine are administered with valproate, at least some of the effects of valproate are mitigated. Perhaps most importantly, the beta-hydroxybutyrate concentration in plasma and the free CoA and acetyl CoA levels in liver do not fall so low. Cotreatment with carnitine alone was without effect. Findings support the CoA depletion mechanism of valproate inhibition of beta-oxidation and other CoA- and acetyl CoA-requiring enzymic reactions and stress the role of carnitine in the regulation of CoA synthesis at the site of action of pantothenate kinase.
Synthesis of phospholipids
7. Pantothenic acid and its derivatives protect Ehrlich ascites tumor cells against lipid peroxidation.
Slyshenkov VS, Rakowska M, Moiseenok AG, Wojtczak L. Nencki Institute of Experimental Biology, Warsaw, Poland.
Free Radic Biol Med. 1995 Dec;19(6):767-72. Erratum in:Free Radic Biol Med 1996;20(3):493.
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.
8. Topical use of dexpanthenol in skin disorders.
Ebner F, Heller A, Rippke F, Tausch I. Technical University of Munich, Allershausen, Germany. email@example.com
Am J Clin Dermatol. 2002;3(6):427-33.
Pantothenic acid is essential to normal epithelial function. It is a component of coenzyme A, which serves as a cofactor for a variety of enzyme-catalyzed reactions that are important in the metabolism of carbohydrates, fatty acids, proteins, gluconeogenesis, sterols, steroid hormones, and porphyrins. The topical use of dexpanthenol, the stable alcoholic analog of pantothenic acid, is based on good skin penetration and high local concentrations of dexpanthenol when administered in an adequate vehicle, such as water-in-oil emulsions. Topical dexpanthenol acts like a moisturizer, improving stratum corneum hydration, reducing transepidermal water loss and maintaining skin softness and elasticity. Activation of fibroblast proliferation, which is of relevance in wound healing, has been observed both in vitro and in vivo with dexpanthenol. Accelerated re-epithelization in wound healing, monitored by means of the transepidermal water loss as an indicator of the intact epidermal barrier function, has also been seen. Dexpanthenol has been shown to have an anti-inflammatory effect on experimental ultraviolet-induced erythema. Beneficial effects of dexpanthenol have been observed in patients who have undergone skin transplantation or scar treatment, or therapy for burn injuries and different dermatoses. The stimulation of epithelization, granulation and mitigation of itching were the most prominent effects of formulations containing dexpanthenol. In double-blind placebo-controlled clinical trials, dexpanthenol was evaluated for its efficacy in improving wound healing. Epidermal wounds treated with dexpanthenol emulsion showed a reduction in erythema, and more elastic and solid tissue regeneration. Monitoring of transepidermal water loss showed a significant acceleration of epidermal regeneration as a result of dexpanthenol therapy, as compared with the vehicle. In an irritation model, pretreatment with dexpanthenol cream resulted in significantly less damage to the stratum corneum barrier, compared with no pretreatment. Adjuvant skin care with dexpanthenol considerably improved the symptoms of skin irritation, such as dryness of the skin, roughness, scaling, pruritus, erythema, erosion/fissures, over 3 to 4 weeks. Usually, the topical administration of dexpanthenol preparations is well tolerated, with minimal risk of skin irritancy or sensitization.
9. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study.
Schmuth M, Wimmer MA, Hofer S, Sztankay A, Weinlich G, Linder DM, Elias PM, Fritsch PO, Fritsch E. Department of Dermatology, University of Innsbruck, Austria. firstname.lastname@example.org
Br J Dermatol. 2002 Jun;146(6):983-91.
BACKGROUND: Radiation dermatitis is a common side-effect of radiation therapy, but there is no current consensus about its appropriate therapy. OBJECTIVES: To compare treatment with topical 0.1% methylprednisolone vs. 0.5% dexpanthenol in a cohort of patients undergoing fractionated radiation therapy for breast cancer. METHODS: In a randomized, double-blind design, treatment was initiated at the beginning of radiation therapy and continued for 2 weeks after termination of radiation. Outcomes were compared by three different measures: clinical (symptom score), functional (transepidermal water loss, TEWL) and subjective (quality of life, QOL). RESULTS: In a preliminary cohort of untreated patients undergoing radiation therapy, clinical signs and TEWL levels increased progressively during radiation therapy, reaching highest values at 5 and 4 weeks, respectively. Although neither topical treatment reduced the incidence of radiation dermatitis, both delayed the emergence of greatest clinical and TEWL scores until approximately 6 and 5 weeks, respectively. With topical corticosteroids, clinical symptoms and TEWL were less pronounced than with dexpanthenol. Whereas general QOL improved after completion of radiation therapy, skin-related QOL declined. However, the skin-related QOL decline could be at least in part reversed by use of topical corticosteroid vs. dexpanthenol-containing emollient. CONCLUSIONS: We provide evidence that prophylactic and ongoing use of topical therapy with either topical corticosteroid or a dexpanthenol-containing emollient ameliorates, but does not prevent radiation dermatitis. Our data suggest, but do not prove, a benefit of a topical corticosteroid vs. a dexpanthenol-containing emollient. Further controlled studies with larger cohorts will be needed to determine optimal forms of topical therapy for radiation dermatitis.
10. Effect of pantothenic acid and ascorbic acid supplementation on human skin wound healing process. A double-blind, prospective and randomized trial.
Vaxman F, Olender S, Lambert A, Nisand G, Aprahamian M, Bruch JF, Didier E, Volkmar P, Grenier JF. INSERM U 61, Hospices Civils, Strasbourg, France.
Eur Surg Res. 1995;27(3):158-66.
This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the would healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars.
11. Role of pantothenic and ascorbic acid in wound healing processes: in vitro study on fibroblasts.
Lacroix B, Didier E, Grenier JF. INSERM Unite 61-Service de Chirurgie B, Hopital Civil, Strasbourg.
Int J Vitam Nutr Res. 1988;58(4):407-13.
In order to analyze the possible role of pantothenic acid (PA) and ascorbic acid (AA) in wound healing processes, the effects of these vitamins upon the growth of fibroblasts, obtained from human fetal skin or foreskin, were studied. Cell proliferation, protein synthesis and protein release were evaluated. The rate of cell growth remained identical when PA or AA were added to the culture medium. PA increased the basal incorporation of 14C proline into precipitated material while AA did not modify this action. However, when cultures were incubated with PA and AA, the release of intracellular protein into the culture medium increased. These results suggest that the combined use of these two vitamins might be of interest in postsurgical therapy and in wound healing.
12. Effects of supplemental pantothenic acid on wound healing: experimental study in rabbit.
Aprahamian M, Dentinger A, Stock-Damge C, Kouassi JC, Grenier JF.
Am J Clin Nutr. 1985 Mar;41(3):578-89.
The effect of pantothenic acid supplementation and deficiency on wound healing was investigated over a one month postoperative period in rabbits. The supplemented group was injected with pentothenate (20 mg/kg of body weight/24 h) for three weeks and compared to a placebo group (0.5 ml of distilled water). Deficient animals were fed with a pantothenate free diet also for three weeks. These three experimental groups were matched against a control group. The degree of wound healing was determined by the mean of postoperative breaking strength and wound fibroblast population changes. Pantothenic acid urinary excretion measured by gas chromatography served as control of pantothenate consumption. With regard to these three parameters no significant difference has been found between placebo and controls. The average urinary elimination in the pantothenic acid group was significantly higher as far as the pantothenate supplemented group was concerned, while the deficient group showed no significant decrease when compared to controls. Chronic pre- and postoperative pantothenic acid supplementation significantly increased aponeurosis strength after surgery; it improved slightly, but not significantly the strength of the skin. Furthermore, the fibroblast content of the scar became significantly greater during the fibroblast proliferation phase after pantothenic supplementation. These data suggest that pantothenic acid induces an accelerating effect of the normal healing process. The mechanism responsible for this improvement seems to be an increase in cellular multiplication during the first postoperative period. But the exact intimate mechanism of the beneficial effect of pantothenate remains unclear.