Potential neuroprotective effect oft-butylhydroquinone against neurotoxicity?Induced by 1-methyl-4-(2?-methylphenyl)-1,2,3,6-tetrahydropyridine (2?-methyl-MPTP) in mice (original) (raw)

2005, Journal of Biochemical and Molecular Toxicology

Dopaminergic damage inducing Parkinson's disease (PD) is ubiquitous neurodegenerative disorder, characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathways. The etiology and pathogenic factors implicated in dopaminergic damage are still unexplored to develop causal therapeutic strategies aimed to halt its progressive loss. The neurotoxicity induced by 1-methyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine (2 CH 3-MPTP), which is more potent neurotoxic than MPTP in mice, is one of the most valuable models for analyzing pathological feature of dopaminergic damage. Herein, we investigated the neuroprotective effect of the potent antioxidant tertiary butylhydroquinone (TBHQ) against 2'CH3-MPTP-induced neurotoxicity in mice as well as the possible mechanism underlying such neurotoxicity. Male albino mice were injected with two doses of 2 CH 3-MPTP (20 mg/kg, i.p) for two consecutive days. Animals were killed after 2 weeks from the last dose of 2 CH 3-MPTP. Control animals received 10 mL/kg body weight i.p of distilled water. In both groups, brain stems containing the nigrostriatal pathways were dissected and reduced glutathione (GSH), malonyldialdehyde (MDA) contents, and superoxide dismutase (SOD) activity were estimated. Also, brain stem histopathological and histochemical changes were examined. The results of this study revealed that i.p injection of 2 CH 3-MPTP caused decrease in the brain stem content of GSH. On the other hand, the content of MDA and SOD activity was increased as compared with control groups. Also, 2 CH 3-MPTP showed severe histopathological changes including swelling of cytoplasm, interstitial edema, and complete loss of the neurons with reactive microglial proliferation and gliosis. Furthermore, histochemical examination of brain stem qualitatively showed deple