EFFECT OF KOLAVIRON ON DOPAMINE METABOLISM, BRAIN REDOX STATUS AND MORPHOLOGY IN ROTENONE-INDUCED PARKINSONISM

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by selective degeneration of dopaminergic neurons in the brain. Systemic unilateral infusion of rotenone reproduces neurochemical and neuropathological features of Parkinsonism in rats. The aim of this research is to evaluate the effect of kolaviron, a biflavonoid extract from Garcinia kola seeds, on dopamine metabolism, redox homeostasis and morphology of brains of rats exposed to rotenone with a view to ascertaining its protective potential against PD. Fifty-Six animals were divided into seven groups with eight animals per group. Group A served as control while group B was administered rotenone (1.5 mg/kg, 6 times within 48 h). Groups C and D were pre-treated with kolaviron (100 and 200 mg/kg, respectively) for 7 days and group E with ubiquinone (1 ml/kg) for 2 days before administering rotenone. Groups F and G were administered kolaviron (100 and 200 mg/kg, respectively) alone. Animals were observed for neurological deficits 24 h after rotenone administration, after which they were sacrificed and the brain and serum processed for biochemical assays and histopathological evaluation. Activity of glutathione peroxidase, tyrosine hydroxylase, xanthine oxidase, monoamine oxidase, myeloperoxidase as well as dopamine and protein carbonyl levels were evaluated. Results showed decreased turnover of dopamine as a result of rotenone administration as observed in the depletion of cortical, striatal and hippocampal dopamine levels. Rotenone administration also caused the suppression of tyrosine hydroxylase activity and increase in monoamine oxidase activity. These rotenone induced changes were significantly reversed by treatment with kolaviron (P<0.05). Also, rotenone significantly elevated the activities of myeloperoxidase and xanthine oxidase in cortex, striatum and hippocampus of the brains of rotenone intoxicated animals as compared to the control (P<0.05). Kolaviron significantly reversed these negative effects in all the brain regions. In conclusion, the results showed that kolaviron was protective against rotenone-induced neuronal damage by counteracting the suppression of dopamine production as well as ameliorating oxidative stress and histopathological alterations and might therefore be effective in the treatment of Parkinson’s disease.