In the present study, we evaluated the effect of melatonin, a well-known free radical scavenger and neuroprotector, against rotenone-induced oxidative stress in a hemiparkinsonian rat model. The effect of melatonin on glutathione (GSH) depletion caused by unilateral, intranigral infusion of rotenone was investigated employing a spectrofluorimetric procedure. We also studied the effect of melatonin on rotenone-induced changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase in the cytosolic fractions of substantia nigra (SN), employing spectrophotometric procedures. Rotenone-induced hydroxyl radicals (*OH) in the isolated mitochondria, as measured employing a sensitive HPLC-electrochemical method, were significantly scavenged by melatonin. Melatonin treatment restored the rotenone-induced decrease in GSH level and changes in antioxidant enzyme (SOD and catalase) activities in the SN. Our results strongly indicate melatonin's beneficial use in Parkinson's disease therapy as an antioxidant.

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Mitochondrial complex‐I dysfunction has been observed in patients of Huntington’s disease (HD). We assessed whether such a defect is present in the 3‐nitropropionic acid (3‐NP) model of HD. Rats treated with 3‐NP (10–20 mg/kg i.p., for 4 days) exhibited weight loss, gait abnormalities, and striatal lesions with increased glial fibrillary acidic protein immunostaining on fifth and ninth days, while increase in striatal dopamine and loss of tyrosine hydroxylase immunoreactivity were observed on fifth day following treatment. We report for the first time a dose‐dependent reduction in complex‐I activity in the cerebral cortex when analyzed spectrophotometrically and by blue native‐polyacrylamide gel electrophoresis following 3‐NP treatment. The citrate synthase normalized activities of mitochondrial complex‐I, ‐II, ‐(I + III) and ‐IV were decreased in the cortex of 3‐NP treated rats. In addition, succinate driven State 3 respiration was also significantly inhibited in vivo and in the isolated mitochondria. These findings taken together with the observation of a significant decrease in vivo but not in vitro of State 3 respiration with NAD+‐linked substrates, suggest complex‐I dysfunction in addition to irreversible inhibition of complex‐II and succinate dehydrogenase activity as a contributing factor in 3‐NP‐induced cortico‐striatal lesion.

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