Antioxidant Effect of Alpha-Lipoic Acid in 6-Hydroxydopamine Unilateral Intrastriatal Injected Rats

Abstract

The toxin 6-hydroxydopamine (6-OHDA) is a highly oxidizable dopamine (DA) analog that is widely used for reproducing several cell processes identified in Parkinson’s disease (PD). Due to the close similarity of its neurotoxic mechanism to those of DA, it is suitable as a model for testing the effects of potentially neuroprotective drugs. This study aimed to evaluate the effect of alpha-lipoic acid (LA) on brain oxidative stress (OS) in unilateral intrastriatal (6-OHDA) injected rats. Forty male Wistar rats, four months old (220−260 g), were evaluated. Half of them received LA (35 mg/kg i.p.) from the start to the end of the experiment. On day 2 of the trial, ten LA-supplemented rats and ten non-LA-supplemented rats were subjected to the apomorphine test. Brain homogenates were evaluated for thiobarbituric acid-reactive substances (TBARS) and glutathione peroxidase (GPx) activity. The same evaluation procedures were repeated on day 14 with the remaining animals. An increased TBARS level and decreased GPx activity, suggestive for OS, were recorded in homogenates on day 14 vs. day 2 of the experiment in the 6-OHDA treated rats. The simultaneous application of LA mitigated these changes. Our study demonstrates that the low dose of LA could be of value for decreasing the OS of the neurotoxic 6-OHDA, supporting the need for further studies of the benefit of LA treatment in PD.

Keywords

• alpha-lipoic acid
• oxidative stress
• 6-hydroxydopamine
• glutathione peroxidase
• lipid peroxidation
• parkinson’s disease