the anti-parkinsonism effects of katp channel blockade in the 6-hydroxydopamine-induced animal model: the role of oxidative stress

Introduction: studies suggest that atp-sensitive potassium (katp) channels are a potential pharmacotherapeutic target for neuroprotection in neurodegenerative diseases. the current study aimed at evaluating the effect of pretreatment with glibenclamide (glib) and b vitamins supplement on the severity of behavioral symptoms in 6-hydroxydopamine (ohda)-induced parkinsonism. also malondialdehyde (mda) concentration was measured in the blood and brain suspensions to find probable neuroprotective mechanism of glib. methods: the 6-ohda was injected into striatum of rats by stereotaxic surgery. treatment with glib and b vitamins was started before the surgery and continued up to 3 weeks after that. development and severity of parkinsonism were evaluated by conventional behavioral tests. mda values were measured spectrophotometrically using thiobarbituric acid and mda standard curve. results: pretreatments with glib, at both doses of 1 and 5 mg/kg or b vitamins significantly ameliorated severity of the behavioral symptoms. pretreatment with a combination of glib and b vitamins was more effective than pretreatment with glib or b vitamins alone. also, pretreatment with b vitamins, glib, or a combination of them reduced mda concentration in the brain suspensions. decrease in mda concentration in the group of rats that received a combination of b vitamins and glib was more prominent than that of the glib groups. conclusion: as severity of the behavioral symptoms in the 6-ohda-induced parkinsonism reflects the degree of the lesion in substantia nigra (sn) dopaminergic neurons, it is suggested that glib pretreatment has neuroprotective effect against 6-ohda-induced neurotoxicity. the current study data also showed that this effect may be mediated by antioxidant effect of glib.