Oxidative stress resulting from enhanced free radical formation and/or a defect in antioxidant defenses has been implicated in the pathogenesis of experimental diabetic neuropathy. In the present study, we have investigated the effect of α- lipoic acid a potent free radical scavenger on glycemic control, oxidative stress and antioxidant enzymes of sciatic nerve in streptozotocin (STZ)-induced diabetic neuropathy model in rats. This study was carried out on 120 male rats. All rats were divided into six main equal groups, 20 animals each. Group I (control group): received no drugs, Group II (diabetic group) received a single dose of streptozotocin (STZ) (50mg/kg i.p.) for the induction of diabetes, Group III (normal α-Lipoic acid-treated group), Group IV (diabetic alpha-Lipoic acid -treated group), Group V (diabetic insulin- treated group), Group VI (diabetic alpha-Lipoic acid and insulin-treated group). Eight weeks after diabetes induction therapeutic treatment with α-lipoic acid (54 mg/kg body weight i.p daily) and insulin (2U s.c daily) were given either alone or in combination and continued for six weeks. Equivalent volumes of saline were given subcutaneously to the rats in the other diabetic and non diabetic control groups. Blood samples and sciatic nerve tissues were collected from all animal groups two times at 4 and 6 weeks from the onset of treatment for determination of serum glucose and nitric oxide in addition to sciatic nerve L-malondialdehyde (L- MDA) and antioxidant enzymes(SOD, CAT and GPX) activities. The obtained results revealed that, a significant increase in serum glucose, sciatic nerve L-MDA concentrations and GPX activity with marked reduction in SOD and CAT activities were observed in STZ-induced diabetic neuropathy in rats. Treatment with alpha lipoic acid, insulin and their combination significantly decreased serum glucose and sciatic nerves L-MDA concentrations and significantly increased serum nitric oxide concentration as well as sciatic nerve SOD, CAT and GPX activities. These results suggest that, α-lipoic acid treatment with insulin improved significantly the diabetes-induced deterioration and attenuates the status of antioxidant enzymes and biomarkers of oxidative stress produced by diabetic neuropathy and its complication in diabetes mellitus.
Key words: diabetic neuropathy, sciatic nerve, oxidative stress, antioxidant enzymes.
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