Protective Effect of Alpha Lipoic Acid on Rat Sciatic Nerve Ischemia Reperfusion Damage

Year 2015, Volume: 32 Issue: 2, 196 - 202, 01.04.2015

Ozan Turamanlar Ahmet Songur Oğuz Aslan Özen Murat Yağmurca Cevat Aktaş Sezer Akçer Hakan Mollaoğlu

Abstract

Background: Alpha lipoic acid is a potent antioxidant that plays numerous roles in human health. This study examined the effect of ALA on rat sciatic nerve ischemia reperfusion damage. Aims: Protective effect of alpha lipoic acid (ALA) on sciatic nerve following ischemia-reperfusion in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nerve is proven, we think the damage to the sciatic nerve that has already occurred or might occur in patients for various reasons maybe prevented or stopped by giving ALA in convenient doses. Study Design: Animal experiment. Methods: Forty-two adult male Sprague-Dawley rats (250-300 grams) were used in this study. Rats were randomly divided into six groups including one control (Group 1), one sham (Group 2), two ischemia-reperfusion (Groups 3 and 4) and two treatment groups (Groups5 and 6). Doses of 60 and 100 mg/kg ALA were given (Group 5 and 6) intra peritoneally twice, 1 and 24 hours before the ischemia to each treatment group. Ischemia was carried out the abdominal aorta starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. In immunohistochemical methods, fibronectin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorf microtubes and superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) enzyme activities as well as malondialdehyde (MDA) and nitricoxide (NO) levels were measured. Results: Fibronectin was observed to have increased significantly in the ischemia group; on the other hand, it was observed to have decreased in parallel to the doses in the ALA groups. Biochemical studies showed that SOD and GSHPx declined with ischemia-reperfusion, but the activities of these enzymes were increased in the treatment groups in parallel with the dose. It was found that increased MDA levels with ischemia-reperfusion were decreased in parallel with ALA dose. There were no statistically significant changes in NO. Conclusion: Increased fibronectin observed after ischemia/reperfusion of rat sciatic nerve is reduced after the administration of ALA. This indicates that the function of fibronectin, to reconnect cut nerve segments and regenerate nerves, is more prominent than its function in tissue healing after ischemia. ALA administered before ischemia decreases MDA and increases SOD and GSHPx. We think that ALA may protect against the pathological changes in ischemic nerve and may be used to devise more efficient treatments.

Keywords

Alpha lipoic acid, ischemia-reperfusion, sciatic nerve, rat

References

• 1. Bosquesi PL, Melo TRF, Vizioli EO, Santos JL Dos, Chung MC. Anti-Inflammatory drug design using a molecular hybridization approach. Pharmaceuticals (Internet) 2011;4:1450-74. [CrossRef]
• 2. Gedlicka C, Kornek G V, Schmid K, Scheithauer W. Amelioration of docetaxel/cisplatin induced polyneuropathy by α-lipoicacid. Ann Oncol 2003;14:339-40. [CrossRef]
• 3. Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radic Biol Med 1995;19:227-50. [CrossRef]
• 4. Mitsui Y, Schmelzer JD, Zollman PJ, Mitsui M, Tritschler HJ, Low PA. Alpha-lipoic acid provides neuroprotection from ischemia-reperfusion injury of peripheral nerve. J Neurol Sci 1999;163:11-6. [CrossRef]
• 5. Shaafi S, Afrooz MR, Hajipour B, Dadadshi A, Hosseinian MM, Khodadadi A. Anti-oxidative effect of lipoic Acid in spinal cord ischemia/reperfusion. Med Princ Pract 2011;20:19-22. [CrossRef]
• 6. Hsu SM, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 1981;29:577-80. [CrossRef]
• 7. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenolreagent. J Biol Chem 1951;193:265-75.
• 8. Durak İ, Işik CÜ, Canbolat O, Akyol Ö, Kavutçu M. Adenosine deaminase, 5′ nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. Free Radic Biol Med 1993;15:681-4. [CrossRef]
• 9. Sun YI, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34:497-500.
• 10. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967;70:158-69.
• 11. Draper HH, Hadley M. Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 1989;186:421-31. [CrossRef]
• 12. Sahin K, Sahin N, Yaralioglu S. Effects of vitamin C and vitamin E on lipid peroxidation, blood serum metabolites, and mineral concentrations of laying hens reared at high ambient temperature. Biol Trace Elem Res 2002;85:35-45. [CrossRef]
• 13. Cortas NK, Wakid NW. Determination of inorganic nitrate in serum and urine by a kinetic cadmium-reduction method. Clin Chem 1990;36:1440-3.
• 14. Nacar A, Omeroglu S. Diyabetik nöropatide periferik sinir hücre dışı matriks yapısı. Düzce Tıp Fak Derg 2004;1:42-7.
• 15. Tuttle KR, Anderberg RJ, Cooney SK, Meek RL. Oxidative stress mediates protein kinase C activation and advanced glycation end product formation in a mesangial cell model of diabetes and high protein diet. Am J Nephrol 2009;29:171-80. [CrossRef]
• 16. Nacar A, Elmas Ç, Erdogan D, Omeroglu S. Streptozotosin ile diyabet oluşturulan sıçanlarda siyatik sinirde laminin, tip 4 kollojen ve fibronektin dağılımlarının immunohistokimyasal olarak incelenmesi. Tıp Araşt Derg 2007;5:129-34.
• 17. Bagdatoglu OT, Polat G, Bagdatoglu C, Atik U. Roles of nitric oxide, malondialdehyde, and fibronectin in an experimental peripheral nerve ischemia-reperfusion model. Microsurgery 2006;26:207-11. [CrossRef]
• 18. Senoglu M, Nacitarhan V, Kurutas EB, Senoglu N, Altun I, Atli Y, et al. Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve. J Brachial Plex Peripher Nerve Inj 2009;4:22. [CrossRef]
• 19. Cosar E, Sahin FK, Köken G, Toy H, Basarali K, Büyükbas S. The protective effect of alpha-lipoic acid in experimental ovarian ischaemia-reperfusion injury. Aust N Z J Obstet Gynaecol 2007;47:499-503. [CrossRef]
• 20. Militão GCG, Ferreira PMP, de Freitas RM. Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures. Neurochem Int 2010;56:16-20. [CrossRef]
• 21. Cui X, Zuo P, Zhang Q, Li X, Hu Y, Long J, et al. Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of Ralpha-lipoic acid. J Neurosci Res 2006;84:647-54. [CrossRef]
• 22. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet 1994;344:721-4. [CrossRef]
• 23. Gaunt GL, Duve C. Subcellular distribution of D-amino acıd oxidase and catalase in rat brain. J Neurochem 1976;26:749-59. [CrossRef