Tags

Type your tag names separated by a space and hit enter

Involvement of NADPH oxidase and glutathione in zinc-induced dopaminergic neurodegeneration in rats: similarity with paraquat neurotoxicity.
Brain Res. 2012 Feb 15; 1438:48-64.BR

Abstract

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 (20 mg/kg; i.p.) or PQ (5 mg/kg; i.p.) in the presence and absence of NADPH oxidase inhibitor, apocynin (10 mg/kg; i.p.) and a GSH precursor, N-acetyl cysteine (NAC; 200 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.

Authors+Show Affiliations

Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR), Lucknow-226001, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22244881

Citation

Kumar, Ashutosh, et al. "Involvement of NADPH Oxidase and Glutathione in Zinc-induced Dopaminergic Neurodegeneration in Rats: Similarity With Paraquat Neurotoxicity." Brain Research, vol. 1438, 2012, pp. 48-64.
Kumar A, Singh BK, Ahmad I, et al. Involvement of NADPH oxidase and glutathione in zinc-induced dopaminergic neurodegeneration in rats: similarity with paraquat neurotoxicity. Brain Res. 2012;1438:48-64.
Kumar, A., Singh, B. K., Ahmad, I., Shukla, S., Patel, D. K., Srivastava, G., Kumar, V., Pandey, H. P., & Singh, C. (2012). Involvement of NADPH oxidase and glutathione in zinc-induced dopaminergic neurodegeneration in rats: similarity with paraquat neurotoxicity. Brain Research, 1438, 48-64. https://doi.org/10.1016/j.brainres.2011.12.028
Kumar A, et al. Involvement of NADPH Oxidase and Glutathione in Zinc-induced Dopaminergic Neurodegeneration in Rats: Similarity With Paraquat Neurotoxicity. Brain Res. 2012 Feb 15;1438:48-64. PubMed PMID: 22244881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of NADPH oxidase and glutathione in zinc-induced dopaminergic neurodegeneration in rats: similarity with paraquat neurotoxicity. AU - Kumar,Ashutosh, AU - Singh,Brajesh Kumar, AU - Ahmad,Israr, AU - Shukla,Smriti, AU - Patel,Devendra Kumar, AU - Srivastava,Garima, AU - Kumar,Vinod, AU - Pandey,Haushila Prasad, AU - Singh,Chetna, Y1 - 2011/12/20/ PY - 2011/08/24/received PY - 2011/12/12/revised PY - 2011/12/13/accepted PY - 2012/1/17/entrez PY - 2012/1/17/pubmed PY - 2012/7/18/medline SP - 48 EP - 64 JF - Brain research JO - Brain Res VL - 1438 N2 - 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 (20 mg/kg; i.p.) or PQ (5 mg/kg; i.p.) in the presence and absence of NADPH oxidase inhibitor, apocynin (10 mg/kg; i.p.) and a GSH precursor, N-acetyl cysteine (NAC; 200 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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/22244881/Involvement_of_NADPH_oxidase_and_glutathione_in_zinc_induced_dopaminergic_neurodegeneration_in_rats:_similarity_with_paraquat_neurotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(11)02229-3 DB - PRIME DP - Unbound Medicine ER -