Nutr Res Pract.  2011 Oct;5(5):421-428.

Effects of alpha-lipoic acid and L-carnosine supplementation on antioxidant activities and lipid profiles in rats

• Kim MY
• Kim EJ
• Kim YN
• Choi C
• Lee BH

Abstract

alpha-Lipoic acid and L-carnosine are powerful antioxidants and are often used as a health supplement and as an ergogenic aid. The objective of this study was to investigate the effects of alpha-lipoic acid and/or L-carnosine supplementation on antioxidant activity in serum, skin, and liver of rats and blood lipid profiles for 6 weeks. Four treatment groups received diets containing regular rat chow diet (control, CON), 0.5% alpha-lipoic acid (ALA), 0.25% alpha-lipoic acid + 0.25% L-carnosine (ALA + LC), or 0.5% L-carnosine (LC). Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and lipid peroxidation products, malondialdehyde (MDA) concentrations, were analyzed in serum, skin, and liver. Blood lipid profiles were measured, including triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C). Skin and liver SOD activities of the ALA and LC groups were higher than those of the CON group (P < 0.05), but serum SOD activity was higher only in the LC group compared to that in the CON group (P < 0.05). Additionally, only liver GSH-Px activity in the LC group was higher than that of the CON and the other groups. Serum and skin MDA levels in the ALA and LC groups were lower than those in the CON group (P < 0.05). Serum TG and TC in the ALA and ALA + LC groups were lower than those in the CON and LC groups (P < 0.05). The HDL-C level in the LC group was higher than that in any other group (P < 0.05). LDL-C level was lower in the ALA + LC and LC groups than that in the CON group (P < 0.05). Thus, alpha-lipoic acid and L-carnosine supplementation increased antioxidant activity, decreased lipid peroxidation in the serum, liver, and skin of rats and positively modified blood lipid profiles.

Keyword

alpha-Lipoic Acid; L-carnosine; antioxidant activity; glutathione peroxidase; superoxide dism

MeSH Terms

Animals
Antioxidants
Cholesterol
Cholesterol, HDL
Cholesterol, LDL
Diet
Glutathione Peroxidase
Lipid Peroxidation
Lipoproteins
Liver
Malondialdehyde
Rats
Skin
Superoxide Dismutase
Thioctic Acid
Triglycerides
Antioxidants
Cholesterol
Cholesterol, HDL
Cholesterol, LDL
Glutathione Peroxidase
Lipoproteins
Malondialdehyde
Superoxide Dismutase
Thioctic Acid
Triglycerides

Reference

1. Busby RW, Schelvis JP, Yu DS, Babcock GT, Marletta MA. Lipoic acid biosynthesis: LipA is an iron-sulfur protein. J Am Chem Soc. 1999. 121:4706–4707.

2. Roy S, Packer L. Redox regulation of cell functions by alpha-lipoate: biochemical and molecular aspects. Biofactors. 1998. 7:263–267.

3. Reed LJ. From lipoic acid to multi-enzyme complexes. Protein Sci. 1998. 7:220–224.

4. Liu J. The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Neurochem Res. 2008. 33:194–203.

5. Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol. 1997. 29:315–331.

6. Cakatay U. Pro-oxidant actions of alpha-lipoic acid and dihydrolipoic acid. Med Hypotheses. 2006. 66:110–117.

7. Packer L, Roy S, Sen CK. Alpha-lipoic acid: a metabolic antioxidant and potential redox modulator of transcription. Adv Pharmacol. 1997. 38:79–101.

8. Niijima A, Okui T, Matsumura Y, Yamano T, Tsuruoka N, Kiso Y, Nagai K. Effects of L-carnosine on renal sympathetic nerve activity and DOCA-salt hypertension in rats. Auton Neurosci. 2002. 97:99–102.

9. Morganti P, Bruno C, Guarneri F, Cardillo A, Del Ciotto P, Valenzano F. Role of topical and nutritional supplement to modify the oxidative stress. Int J Cosmet Sci. 2002. 24:331–339.

10. Reeves PG, Nielsen FH, Fahey GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993. 123:1939–1951.

11. Song KH, Lee WJ, Koh JM, Kim HS, Youn JY, Park HS, Koh EH, Kim MS, Youn JH, Lee KU, Park JY. α-Lipoic acid prevents diabetes mellitus in diabetes-prone obese rats. Biochem Biophys Res Commun. 2005. 326:197–202.

12. Thirunavukkarasu V, Nandhini AT, Anuradha CV. Lipoic acid prevents collagen abnormalities in tail tendon of high-fructose-fed rats. Diabetes Obes Metab. 2005. 7:294–297.

13. Lee JC, Kim KH, Ahn SM, Lee HW, Lee BG. Effect of lipoic acid on antioxidant enzyme system in aged hairless mouse skin in vivo. Korean J Dermatol. 2003. 41:Suppl 2. 161.

14. Böhm F, Edge R, Lange L, Truscott TG. Enhanced protection of human cells against ultraviolet light by antioxidant combinations involving dietary carotenoids. J Photochem Photobiol B. 1998. 44:211–215.

15. Böhm F, Edge R, McGarvey DJ, Truscott TG. Beta-carotene with vitamins E and C offers synergistic cell protection against NOx. FEBS Lett. 1998. 436:387–389.

16. Beitner H. Randomized, placebo-controlled, double blind study on the clinical efficacy of a cream containing 5% α-lipoic acid related to photoageing of facial skin. Br J Dermatol. 2003. 149:841–849.

17. Freisleben HJ, Groth N, Fuchs J, Rudolph P, Zimmer G, Herrling T. Penetration of spin-labeled dihydrolipoate into the skin of hairless mice. Modification of epidermal and dermal polarity. Arzneimittelforschung. 1994. 44:1047–1050.

18. Podda M, Rallis M, Traber MG, Packer L, Maibach HI. Kinetic study of cutaneous and subcutaneous distribution following topical application of [7,8-¹⁴C]rac-alpha-lipoic acid onto hairless mice. Biochem Pharmacol. 1996. 52:627–633.

19. Boldyrev AA, Severin SE. The histidine-containing dipeptides, carnosine and anserine: distribution, properties and biological significance. Adv Enzyme Regul. 1990. 30:175–194.

20. Decker EA, Livisay SA, Zhou S. A re-evaluation of the antioxidant activity of purified carnosine. Biochemistry (Mosc). 2000. 65:766–770.

21. Lee YT, Hsu CC, Lin MH, Liu KS, Yin MC. Histidine and carnosine delay diabetic deterioration in mice and protect human low density lipoprotein against oxidation and glycation. Eur J Pharmacol. 2005. 513:145–150.

22. Yamano T, Niijima A, Iimori S, Tsuruoka N, Kiso Y, Nagai K. Effect of L-carnosine on the hyperglycemia caused by intracranial injection of 2-deoxy-D-glucose in rats. Neurosci Lett. 2001. 313:78–82.

23. Prieto-Hontoria PL, Pérez-Matute P, Fernández-Galilea M, Barber A, Martínez JA, Moreno-Aliaga MJ. Lipoic acid prevents body weight gain induced by a high fat diet in rats: effects on intestinal sugar transport. J Physiol Biochem. 2009. 65:43–50.

24. Dicter N, Madar Z, Tirosh O. Alpha-lipoic acid inhibits glycogen synthesis in rat soleus muscle via its oxidative activity and the uncoupling of mitochondria. J Nutr. 2002. 132:3001–3006.

25. Ramos LF, Kane J, McMonagle E, Le P, Wu P, Shintani A, Ikizler TA, Himmelfarb J. Effects of combination tocopherols and alpha lipoic acid therapy on oxidative stress and inflammatory biomarkers in chronic kidney disease. J Ren Nutr. 2011. 21:211–218.

26. Yi HC. Supplementation to diet on muscle carnosine and blood chemical indices of rats. 2006. Seoul: Chung-Ang University;[master's thesis].

27. Kim YP, Lee SC. Hayaishi O, Imamura S, Miyachi Y, editors. Superoxide dismutase activities in the human skin. The Biological Role of Reactive Oxygen Species in Skin. 1987. Tokyo: University of Tokyo Press;225–320.

28. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974. 47:469–474.

29. Flohé L, Günzler WA. Assays of glutathione peroxidase. Methods Enzymol. 1984. 105:114–121.

30. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979. 95:351–358.

31. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957. 28:56–63.

32. Shen QW, Jones CS, Kalchayanand N, Zhu MJ, Du M. Effect of dietary alpha-lipoic acid on growth, body composition, muscle pH, and AMP-activated protein kinase phosphorylation in mice. J Anim Sci. 2005. 83:2611–2617.

33. Song KH, Youn JY, Nam Koong C, Shin MJ, Ryu JW, Park HS, Kim MS, Park JY, Lee KU. Anti-obesity effects of α-lipoic acid in OLETF Rats. J Korean Diabetes Assoc. 2002. 26:460–468.

34. Tamaki N, Funatsuka A, Fujimoto S, Hama T. The utilization of carnosine in rats fed on a histidine-free diet and its effect on the levels of tissue histidine and carnosine. J Nutr Sci Vitaminol (Tokyo). 1984. 30:541–551.

35. Voss P, Siems W. Clinical oxidation parameters of aging. Free Radic Res. 2006. 40:1339–1349.

36. Liu WH, Liu TC, Yin MC. Beneficial effects of histidine and carnosine on ethanol-induced chronic liver injury. Food Chem Toxicol. 2008. 46:1503–1509.

37. Arivazhagan P, Thilakavathy T, Panneerselvam C. Antioxidant lipoate and tissue antioxidants in aged rats. J Nutr Biochem. 2000. 11:122–127.

38. Sahin M, Sağdiç G, Elmas O, Akpinar D, Derin N, Aslan M, Agar A, Alicigüzel Y, Yargiçoğlu P. Effect of chronic restraint stress and alpha-lipoic acid on lipid peroxidation and antioxidant enzyme activities in rat peripheral organs. Pharmacol Res. 2006. 54:247–252.

39. Akpinar D, Yargiçoğlu P, Derin N, Alicigüzel Y, Ağar A. The effect of lipoic acid antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress. Physiol Res. 2008. 57:893–901.

40. Saygili EI, Konukoglu D, Papila C, Akcay T. Levels of plasma vitamin E, vitamin C, TBARS, and cholesterol in male patients with colorectal tumors. Biochemistry (Mosc). 2003. 68:325–328.

41. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990. 186:407–421.

42. Zulkhairi A, Zaiton Z, Jamaluddin M, Sharida F, Mohd TH, Hasnah B, Nazmi HM, Khairul O, Zanariyah A. Alpha lipoic acid possess dual antioxidant and lipid lowering properties in atherosclerotic-induced New Zealand White rabbit. Biomed Pharmacother. 2008. 62:716–722.

43. Dobrota D, Fedorova T, Stvolinsky S, Babusikova E, Likavcanova K, Drgova A, Strapkova A, Boldyrev A. Carnosine protects the brain of rats and Mongolian gerbils against ischemic injury: after-stroke-effect. Neurochem Res. 2005. 30:1283–1288.

44. Mehmetçik G, Ozdemirler G, Koçak-Toker N, Cevikbaş U, Uysal M. Role of carnosine in preventing thioacetamide-induced liver injury in the rat. Peptides. 2008. 29:425–429.

45. Long J, Gao F, Tong L, Cotman CW, Ames BN, Liu J. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. Neurochem Res. 2009. 34:755–763.

46. Ford I, Cotter MA, Cameron NE, Greaves M. The effects of treatment with α-lipoic acid or evening primrose oil on vascular hemostatic and lipid risk factors, blood flow, and peripheral nerve conduction in the streptozotocin-diabetic rat. Metabolism. 2001. 50:868–875.

47. Ziegler D, Nowak H, Kempler P, Vargha P, Low PA. Treatment of symptomatic diabetic polyneuropathy with the antioxidant α-lipoic acid: a meta-analysis. Diabet Med. 2004. 21:114–121.

48. Ichikawa T, Liang J, Kitajima S, Koike T, Wang X, Sun H, Morimoto M, Shikama H, Watanabe T, Yamada N, Fan J. Macrophage-derived lipoprotein lipase increases aortic atherosclerosis in cholesterol-fed Tg rabbits. Atherosclerosis. 2005. 179:87–95.

49. Marangon K, Devaraj S, Tirosh O, Packer L, Jialal I. Comparison of the effect of alpha-lipoic acid and alpha-tocopherol supplementation on measures of oxidative stress. Free Radic Biol Med. 1999. 27:1114–1121.

50. Butler JA, Hagen TM, Moreau R. Lipoic acid improves hypertriglyceridemia by stimulating triacylglycerol clearance and downregulating liver triacylglycerol secretion. Arch Biochem Biophys. 2009. 485:63–71.

51. Rashid I, van Reyk DM, Davies MJ. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett. 2007. 581:1067–1070.

52. Li AC, Glass CK. The macrophage foam cell as a target for therapeutic intervention. Nat Med. 2002. 8:1235–1242.

53. Wolford ST, Schroer RA, Gohs FX, Gallo PP, Brodeck M, Falk HB, Ruhren R. Reference range data base for serum chemistry and hematology values in laboratory animals. J Toxicol Environ Health. 1986. 18:161–188.

54. Cremer DR, Rabeler R, Roberts A, Lynch B. Safety evaluation of alpha-lipoic acid (ALA). Regul Toxicol Pharmacol. 2006. 46:29–41.