title: Involvement of nitric oxide in maneb- and paraquat-induced Parkinson's disease phenotype in mouse: is there any link with lipid peroxidation?
abstract: The study aimed to investigate the involvement of nitric oxide (NO) in maneb (MB)- and paraquat (PQ)-induced Parkinson's disease (PD) phenotype in mouse and its subsequent contribution to lipid peroxidation. Animals were treated intraperitoneally with or without MB and PQ, twice a week for 3, 6 and 9 weeks. In some sets of experiments (9 weeks treated groups), the animals were treated intraperitoneally with or without inducible nitric oxide synthase (iNOS) inhibitor-aminoguanidine, tyrosine kinase inhibitor-genistein, nuclear factor-kappa B (NF-kB) inhibitor-pyrrolidine dithiocarbamate (PDTC) or p38 mitogen activated protein kinase (MAPK) inhibitor-SB202190. Nitrite content and lipid peroxidation were measured in all treated groups along with respective controls. RNA was isolated from the striatum of control and treated mice and reverse transcribed into cDNA. RT-PCR was performed to amplify iNOS mRNA and western blot analysis was done to check its protein level. MB- and PQ-treatment induced nitrite content, expressions of iNOS mRNA and protein and lipid peroxidation as compared with respective controls. Aminoguanidine resulted in a significant attenuation of iNOS mRNA expression, nitrite content and lipid peroxidation demonstrating the involvement of nitric oxide in MB- and PQ-induced lipid peroxidation. Genistein, SB202190 and PDTC reduced the expression of iNOS mRNA, nitrite content and lipid peroxidation in MB- and PQ-treated mouse striatum. The results obtained demonstrate that nitric oxide contributes to an increase of MB- and PQ-induced lipid peroxidation in mouse striatum and tyrosine kinase, p38 MAPK and NF-kB regulate iNOS expression.
authors.affiliation: Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Mahatma Gandhi Marg, Lucknow, UP, India.
authors.forename: Satya Prakash
authors.initials: SP
authors.lastname: Gupta
authors.forename: Suman
authors.initials: S
authors.lastname: Patel
authors.forename: Sharawan
authors.initials: S
authors.lastname: Yadav
authors.forename: Anand Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008344:Maneb / Q000633:toxicity*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009573:Nitrites / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D010575:Pesticides / Q000633:toxicity*; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis; D015290:Second Messenger Systems / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D006146:Guanidines; D009573:Nitrites; D010575:Pesticides; D012333:RNA, Messenger; D008344:Maneb; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D014446:Tyrosine 3-Monooxygenase; D010269:Paraquat; C004479:pimagedine
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