Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats

Document Type: Original Article


1 Department of Biology, Faculty of Science, Firat University, 23119-Elazig, Turkey

2 Department of Biology, Faculty of Science, Bitlis Eren University, 13000-Bitlis, Turkey

3 Department of Chemistry, Faculty of Science, Harran University, 63100-S.Urfa, Turkey

4 Department of Internal Medicine, School of Medicine, Firat University, 23119-Elazig, Turkey


AD. Diabetes and nutrition: the mitochondrial part. J
Nutr 2001; 131:344– 353.
2. Maritim AC, Sanders RA, Watkins JB. Diabetes, oxidative stress, and antioxidants: A review. J Biochemical Mol Toxicol 2003; 17:24- 38.
3. Emilien G, Maloteaux JM , Ponchon M. Pharmacological management of diabetes: recent progress and future perspective of daily drug treatment. Pharmacol Ther 1999; 81: 37-51.
4. Engelgau MM, Geiss LS. The burden of diabetes mellitus. In: Leahy JL, Clark NG, Cefalu WT. editors. Medical Management of Diabetes Mellitus. Mark Dekker, New York: 2000.p.1–17.
5. Biessels GJ, Smale S, Simone EJ, Kamal DE, Gispen WH. The effect of gamma-linolenic acid–alpha-lipoic acid on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats. J Neurol Sci 2001; 182:99–106.
6. Shin CS, Lee MK, Park KS, Kim SY, Cho BY, Lee HK,
et al.
Insulin restores fatty acid composition earlier in liver microsomes than erythrocyte membranes in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 1995; 29:93-98.
7. Van BilsenM, DeVries JE, VanderVusse GJ. Long-term effects of fatty acids on cell viability and gene expression of neonatal cardiac myocytes. Prostaglandins Leukot Essent Fatty Acids 1997; 57: 39-45.
8. Van der Vusse GJ, Glatz JFC, Van Nieuwenhoven FA, Reneman RS, Bassingthwaighte JB. Transport of long-chain fatty acids across the muscular endothelium. Adv Exp Med Biol 1998; 441: 181-191.
9. Borkman M, Storlien LH, Pan DA, Jenkins AB, Chisholm DJ, Campel LV. The relation between insulin sensitivity and the fatty acid composition of skeletal muscle. New Eng J Med 1993; 328:238- 244.
10. Fla´via RC, Seelaender MCL. Liver denervation affects hepatocyte mitochondrial fatty transport capacity. Cell Biochem Funct 2004; 22:9–17.
11. Poisson JPG, Cunnane SC. Long-chain fatty acid metabolim in fasting and diabetes-relation between altered desaturase activity and fatty-acid composition. J Nutr Biochem 1991; 2:60-70.
12. Mimouni V, Poisson JP. Altered desaturase activities and fatty acid composition in liver microsomes of spontaneously diabetic Wistar BB rat. Biochim Biophys Acta 1992; 1123:296-302.
13. Douillet C, Ciavatti M. Effect of vitamin E treatment on tissue fatty acids and cholesterol content in experimental diabetes. J Nutr Biochem 1995; 29:319-326.
14. Reche P, Perham RN. Structure and selectivity in post-translational modification: attaching the biotinyl-lysine and lipoyl-lysine swinging arms in multifunctional enzymes. EMBO J 1999; 18: 2673–2682.
15. Fang YZ, Yang S, Wu GY. Free radicals, antioxidants, and nutrition Nutrition 2002; 18:872-879.
16. Jacob S, Streeper RS, Fogt DL, Hokama JY, Tritschler HJ, Dietze GJ,
et al.
The antioxidant alpha-lipoic acid enhances insulin-stimulated glucose metabolism in insulin-resistant rat skeletal muscle. Diabetes 1996; 45:1024-1029.
17. Slater TF. Free radical mechanisms in tissue injury. Biochem J 1984; 222:1–15.
18. Fang YZ, Yang S, Wu GY. Free radicals, antioxidants, and nutrition. Nutrition 2002; 18:872-879.
19. Huang HY, Appel LJ, Croft KD, Miller ER, Mori TA, Puddey IB. Effects of vitamin C and vitamin E on
in vivo
lipid peroxidation: results of a randomized controlled trial. Am J Clin Nutr 2002; 76:549-555.
20. Orzechowski A. Dietary prophylaxis as an alternative method for the prevention of the development of insulin resistance. Med Weter 2003; 59:767-772.
21. Folch JM, Lees M, Sloane-Stanley GH. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957; 226:497-509.
22. Christie WW. Gas Chromatography and Lipids. Glaskow: The Oil Press; 1992.p.302.
23. Katsanidus E, Addis PB. Novel HPLC analysis of tocopherols, tocotrienols, and cholesterol in tissue. Free Rad Biol Med 1999; 27:1137–1140.
24. Bragagnolo N, Rodriguez-Amaya DB. Comparison of the cholesterol content of Brazilian chicken and quail eggs. J Food Comp Analysis ?? 2003; 16: 147-153.
25. Serada TJ, Mant CT, Hodges RS. Use of sodium perchlorate at low pH for peptide separatios by reversed-phase liquid chromatography. Influence of perchlorate ion on apparent hydrophilicity of positively charged amino acid side-chains. J Chromatogr 1997; 776:153-165.
26. Yoshida T. Determination of reduced and oxidized glutathione in erythrocytes by high performance liquid chromatography with ultraviolet absorbance dedection. J Chromatogr B 1996; 678: 157-168.
27. Gallou G, Ruelland A, Legras B, Maugendre D, Allanic H, Cloarec L. Plasma malondialdehyde in type 1 and type 2 diabetic patients. Clin Chim Acta 1993; 214:227–234.
28. Mero N, Syvanne M, Taskinen MR. Postprandial lipid metabolism in diabetes. Atherosclerosis 1998; 141:53-55.
29. Steinberg HO, Baron AD. Vascular function, insulin resistance and fatty acids. Diabetologia 2002; 45:623–634.
30. Paolisso G, D’Amore A, Giugliano D, Ceriello A, Varricchio M, D’Onofrio F. Pharmacologic doses of vitamin E improve insulin action in healthy subjects and non-insulin-dependent diabetic patients. Am J Clin Nutr 1993; 57:650–656.
31. Teupser D, Thiery J, Seidel D. Alpha-tocopherol down-regulates scavenger receptor activity in macrophages. Atherosclerosis
1999; 144:109–115.
32. Ricciarelli R, Zingg JM, Azzi A. Vitamin E reduces the uptake of oxidized LDL by inhibiting CD36 scavenger receptor expression in cultured aortic smooth muscle cells. Circulation 2000; 102: 82–87.
33. Beutler E. Nutritional and metabolic aspects of glutathione. Ann Rew Nutr 1989; 9:287-302.
34. May JM, Qu ZC, Whitesell RR, Cobb CE. Ascorbate recycling in human erythrocytes: Role of GSH in reducing dehydroascorbate. Free Rad Biol Med 1996; 20:543-551.
35. Sies H. Glutathione and its role in cellular functions. Free Rad Biol Med 1999; 27:916–921.
36. Packer L, Witt EH, Tritschler HJ. Alpha-Lipoic acid as a biological antioxidant. Free Rad Biol Med 1995; 19:227-250.
37. Packer L, Tritschler HJ, Wessel K. Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Rad Biol Med 1997; 22:359-378.
38. Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001; 17:888–895.
39. Jacob S, Ruus P, Hermann R, Tritschler HJ, Maerker E, Renn W,
et al.
Oral administration of RAC-alphalipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial. Free Rad Biol Med 1999; 27:309–314.
40. Yilmaz O, Ozkan Y, Yıldırım M, Ozturk AI, Ersan Y. Effects of alpha lipoic acid, ascorbic acid-6-palmitate and fish oil on the glutathione, malonaldehyde and fatty acid levels in erythrocytes of streptozotocin induced diabetic male rats. J Cell Biochem 2002; 86:530-539.
41. Dincer Y, Telci A, Kayali R, Yilmaz IA, Cakatay U, Akcay T. Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme activities in diabetic rats. Clin Exp Pharm Physiol 2002; 29: 281- 284.
42. Powell LA, Warpeha KM, Xu WM, Walker B, Trimble ER. High glucose decreases intracellular glutathione concentrations and upregulates inducible nitric oxide synthase gene expression in intestinal epithelial cells. J Mol Endocrinol 2004; 33:797-803.
43. Baydas G, Donder E, Kiliboz M, Sonkaya E, Tuzcu M, Yasar A,
et al.
Neuroprotection by alpha-lipoic acid in streptozotocin-induced diabetes. Biochem-Moscow 2004; 69:1001-1005.
44. Mekinova D, Chorvathova V, Volkovova K, Staruchova M, Grancicova E, Klvanova J,
et al.
Effect of intake of exogenous vitamin C, Vitamin E and beta carotene on the antioxidative status in kidneys of rats with streptozotocin-induced diabetes. Nahrung 1995; 39:257-261.
45. Leonardo AE, Pereiraa SL, Sprecherb H, Huangam YS. Elongation of long-chain fatty acids. Prog Lipid Res 2004; 43:36–54.
46. Jones BH, Standridge MK, Claycombe KJ, Smith PJ, Moustaı¨d- Moussa N. Glucose induces expression of stearoyl-CoA desaturase in 3T3–L1 adipocytes. Biochem J 1998; 335:405–408.
47. Legrand P, Bensadoun A. Stearyl-CoA desaturase activity in cultured rat hepatocytes. Biochim Biophys Acta 1991; 1086:89–94.
48. Ntambi JM. Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 1999; 40:1549-1558.
49. Quartacci MF, Cosi E, Navari-Izzo F. Lipids and NADPH dependent superoxide production in plasma membrane vesicles from roots of wheat grown in excess copper. J Exp Bot 2000; 52:77–84.
50. Brenner RR, Bernasconi AM, Garda HA. Effect of experimental diabetes on the fatty acid composition, molecular species of phosphatidyl-choline and physical properties of hepatic microsomal membranes. Prostaglandins Leukot Essent Fatty Acids 2000; 63:167-176.
51. Hu QZ, Ishii E, Nakawa Y. Differential changes in relative levels of arachidonic acid in major phospholipids from rat tissues during the progression of diabtestes. J Biochem 1994; 115:405-408.
52. Mohan IK, Das UN. Effect of L-arginine-nitric oxide system on the metabolism of essential fatty acids in chemical-induced diabetes mellitus. Prostaglandins Leukot Essent Fatty Acids 2000; 62: 35-46.
53. Bassi A, Avogaro A, Crepaldi C, Pavan P, Zambon S, Marin R,
et al.
Short-term diabetic ketosis alters n-6 polyunsaturated fatty acid content in plasma phospholipids. J Clin Endocronol Metabol 1996; 81:1650-1653.
54. Koo JR, Ni ZM, Oviesi F, Vaziri ND. Antioxidant therapy potentiates antihypertensive action of insulin in diabetic rats. Clin Exp Hypertens 2002; 24:333-344.
55. Scott JA, King GL. Title: Oxidative stress and antioxidant treatment in diabetes. Vitamin E & Health Annals. N Y Acad Sci 2004; 1031:204-213.