The current study evidenced hypothesis that
mitochondrial dysfunction-oxidative stress-dependent apoptotic pathways play a critical role in degeneration of dopaminergic neurons in
Parkinson's disease. Model of
rotenone-induced
parkinsonism in rats produced decrease in striatal complex I activity and
reduced glutathione with increase in
nitrites concentration and
caspase-3 activity. This was confirmed by significant correlation of
catalepsy score with neurochemical parameters. Moreover, electron microscopic examination of striatal neurons displayed ultrastructure affection as hyperchromatic nuclei and disrupted mitochondria that are typical features of undergoing apoptosis. Administration of
L-dopa as replacement
therapy, although caused symptomatic improvement in
catalepsy score, but further worsening in neurochemical parameters. Therefore, efforts are not only to improve effect of
L-dopa, but also to introduce drugs provide antiparkinsonian and
neuroprotective effects. In this study, α-
lipoic acid exhibited noticeable
neuroprotective effects by a mechanism via intervention of
mitochondrial dysfunction-oxidative stress-dependent apoptotic pathways. Combination of α-
lipoic acid efficiently halting deleterious toxic effects of
L-dopa, revealed normalization of
catalepsy score in addition to amelioration of neurochemical parameters and apparent preservation of striatal ultrastructure integrity, indicating benefit of both symptomatic and neuroprotective
therapy. In conclusion, α-
lipoic acid could be recommended as a disease-modifying
therapy when given with
L-dopa early in course of
Parkinson's disease.