Synergistic Antiparkinsonian Effect of Flunarizine, Glibenclamide and B Vitamins in a Rat 6-Hydroxydopamine Model; The Role of Malondialdehyde

Abstract

Background: The current study evaluated the effects of a combination of flunarizine (flu) a calcium channel blocker, glibenclamide (Glib), a KATP channels blocker and B vitamins (B com) on the behavioral symptoms of 6-hydroxydopamine (6-OHDA)-induced model of Parkinson disease to evaluate the synergistic antiparkinsonian effects of the drugs and supplements. Also the level of malondialdehyde (MDA) was measured in blood and brain suspensions to find probable neuroprotective mechanism of these materials. Methods: 6-OHDA was injected into striatum of rats by stereotaxic surgery. Pretreatment with flu, Glib and B com was started before the surgery and continued to three weeks after the surgery. Development and severity of Parkinson disease were evaluated by the conventional behavioral tests. MDA values were measured spectrophotometrically, using thiobarbituric acid test and the MDA standard curve. Results: Pretreatment with a combination of flu, Glib and B com ameliorated the behavioral symptoms of Parkinson disease. The effect of the combination was significantly more potent than those of flu, Glib or B com, solely. Pretreatment with the combination or using only Glib or B com separately, reduced the level of MDA in blood and brain, significantly. However, the effect of the combination was significantly more potent than those of Glib or B com, solely. Conclusions: Since the severity of the behavioral symptoms in the 6-OHDA-induced model of Parkinson disease reflects the degree of the lesion in substantia nigra (SN) dopaminergic neurons, it is suggested that using the combination had neuroprotective effects. The obtained data suggest a synergistic neuroprotective and antiparkinsonian effect for flu, Glib and B com. At least, a part of this effect was mediated through inhibition of oxidative stress. Keywords: 6-Hydroxydopamine, Flunarizine, Glibenclamide: B Vitamins, Behavioral Symptoms, Malondialdehyde