| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 6264573 | Brain Research | 2012 | 17 Pages |
An association between excessive zinc (Zn) accumulation in brain and incidences of Parkinson's disease (PD) has been shown in several epidemiological and experimental investigations. The involvement of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and glutathione (GSH) in the pathogenesis of PD has also been proposed in a few studies. Despite the implicated role of oxidative stress in PD, the entire mechanism of Zn-induced dopaminergic neurodegeneration has not yet been clearly understood. The present study aimed to investigate the involvement of NADPH oxidase and GSH in Zn-induced dopaminergic neurodegeneration and also to assess its similarity with paraquat (PQ)-induced rat model of PD. Male Wistar rats were treated either with Zn (20Â mg/kg; i.p.) or PQ (5Â mg/kg; i.p.) in the presence and absence of NADPH oxidase inhibitor, apocynin (10Â mg/kg; i.p.) and a GSH precursor, N-acetyl cysteine (NAC; 200Â mg/kg; i.p.) either alone or in combination along with the respective controls. Apocynin and/or NAC pre-treatment significantly alleviated Zn- and PQ-induced changes in neurobehavioral deficits, number of dopaminergic neurons and contents of the striatal dopamine and its metabolites. Apocynin and/or NAC also mitigated Zn- and PQ-induced alterations in oxidative stress, NADPH oxidase activation and cytochrome c release, caspases-9 and -3 activation and CD11b expression. The results obtained thus suggest that Zn induces oxidative stress via the activation of NADPH oxidase and depletion of GSH, which in turn activate the apoptotic machinery leading to dopaminergic neurodegeneration similar to PQ.
⺠Pesticides and metals have been implicated in the pathogenesis of PD. ⺠Zinc is widely considered as a neurodegenerative agent at specific concentration. ⺠Involvement of free radicals and antioxidants has been documented in PD. ⺠Role of NADPH oxidase and GSH has been shown in zinc-induced neurodegeneration.
