The Anti-Parkinsonism Effects of KATP Channel Blockade in the 6-Hydroxydopamine-Induced Animal Model: The Role of Oxidative Stress.

Abstract

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.

• Authors: Hossein Piri, Hashem Haghdoost-Yazdi, Negin Fraidouni, Tahereh Dargahi, Mohamadhosein Yaghoubidoust, Abbas Azadmehr
• Journal: Basic and clinical neuroscience (Basic Clin Neurosci) 2017 May-Jun Vol. 8 Issue 3 Pg. 183-192 ISSN: 2008-126X [Print] Iran
• PMID: 28781726 (Publication Type: Journal Article)