Protective effect of alpha lipoic acid on rat sciatic nerve ischemia reperfusion damage

Lipoic acid (LA), is a compound which is found in many procariotic ve eucaryotik cell types and formed naturally. Lipoic acid, has been used for the treatment of the following conditions: alcohol-dependent liver damage, fungal intoxications, diabetes, glocom, damage by radiation, Chagas disease, neurodegenerative disorders, ischemia-reperfusion damage, heavy metal intoxications and HIV infections for a long time. In this study, protective effect of alpha-lipoic acid (ALA) on sciatic nevre following ischemia-reperfusion (I/R) in rats was investigated by using light microscopy and biochemical methods. Provided that the protective effect of ALA on sciatic nevre is proven, we think the damage of sciatic nerve that have already occured or might occur in the patients due to various reasons may be prevented or stopped by giving ALA in convenient doses.In this study, a total of fourty-two Sprague-Dawney male rats whose weights are 250 to 300 gr were used. Rats were divided into six groups as follows: control (Group 1), sham (Group 2), I/R (Group 3), I/R + 0.5 ml %0.9 NaCl (Group 4), I/R + 60 mg/kg ALA (Grup 5) and I/R + 100 mg/kg ALA (Group 6). Ischemia was carried out the abdominal aort starting from the distal part of the renal vein for two hours followed by reperfusion for three hours. Extracted sciatic nerve tissues were fixed in formaldehyde solution with neutral pH for histopathologic analysis. In histopathologic analysis, vascular congestion and proliferation as well as myelin degenetion was evaluated semiquantitatively using hematoksilen-eosin staining method. In immunohistochemical method, fibronektin immunoreactivity was analyzed. For biochemical analyses, the tissues were taken in eppendorph microtubes and SOD and GSHPx enzyme activities as well as MDA and NO levels were measured. Statistical analyses for histological and biochemical data were done using Shapiro-Wilk, Kruskal?Wallis H and Mann-Whitney U and pearson correlation tests of SPSS 16.0 computer program respectively.As a result of histopatological investigations, vascular congestion and proliferation as well as myelin degeneration were found to be increased significantly in the sciatic nerve tissues of ischemia group; however, these findings were found to have diminished significantly in various degrees depending on the ALA groups by giving ALA (100 mg/kg). Fibronectin, an important component of extracellular matrix in the developing periferic nervous system, was observed to have increased significantly in ischemia group; on the other hand, it was observed to have decreased in paralel to the doses in the ALA given groups.In biochemical analyses; SOD and GSHPx enzyme activities were found to be lower by ischemia, however, in the ALA group being given 100 mg/kg of ALA, SOD and GSHPx enzyme activities were found to have increased. In the ALA given groups, increased MDA levels by I/R was observed to have decreased significantly in a dose-dependent manner. The decreased NO level by I/R, was seen increased in ALA-given groups, though it was not statistically significant.The fact that fibronectin increase observed after ischemia/reperfusion of rat sciatic nerve is reduced after administration of ALA indicates that fibronectin?s function 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 these positive changes show that ALA may protect against the pathological changes in ischemic nerve and may be used to devise more efficient treatments.