title: Effect of monocrotophos, an organophosphorus insecticide, on the striatal dopaminergic system in a mouse model of Parkinson's disease.
abstract: Our earlier study had shown that low concentrations of monocrotophos (MCP) elicited dopaminergic features of Parkinson's disease (PD) in the nematode Caenorhabditis elegans In the present study, the effect of low doses of MCP on the striatal dopaminergic neurons was investigated using the mouse model system. MCP was initially screened for its ability to cause any neurobehavioral deficits and alterations in the dopaminergic system in Swiss albino mice, aged 8 weeks and weighing 25-30 g, with repeated doses at 0.3 and 0.6 mg/kg body weight (b.w.)/day for 7 days and 30 days. Mice were treated with four intraperitoneal injections for every 2 h with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at the dosage of 14 mg/kg b.w. MCP was administered to these mice at the above-mentioned doses for 7 days. Mice administered with MCP alone revealed a significant (p < 0.05) reduction in the dopamine (DA) content at both 7 and 30 days and showed a significant (p < 0.05) increase in neurobehavioral deficits. Interestingly, when MCP was administered for 7 days to MPTP-treated mice, further significant decrease in both DA content and increase in neurobehavioral deficits were apparent. The extent of reactive oxygen species and lipid peroxidation were markedly increased, while the ratio of reduced to oxidized glutathione levels were significantly decreased (p < 0.05) in the treated mice as compared to the control. Significant histopathological alterations and a marked reduction in the number of tyrosine hydroxylase positive cells were evident in striatum of mice treated with higher doses of MCP. These changes were comparable to that seen in mice treated with MPTP and post-administered lower doses of MCP. Our findings suggest that MCP per se has the propensity to induce pathological changes in the dopaminergic neurons as well as augment the degeneration in a compromised nigrostriatal system such as that in PD.
authors.affiliation: Department of Food Protectants and Infestation Control, Council of Scientific and Industrial Research (CSIR)-Central Food Technological Research Institute, Mysore, Karnataka, India.
authors.forename: Shaheen Jafri
authors.initials: SJ
authors.lastname: Ali
authors.affiliation: Department of Food Protectants and Infestation Control, Council of Scientific and Industrial Research (CSIR)-Central Food Technological Research Institute, Mysore, Karnataka, India rajini29@yahoo.com.
authors.forename: Padmanabhan Sharda
authors.initials: PS
authors.lastname: Rajini
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019803:Glutathione Disulfide / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007306:Insecticides / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008999:Monocrotophos / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D007306:Insecticides; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D008999:Monocrotophos; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D019803:Glutathione Disulfide; D004298:Dopamine
keywords: Dopamine; Parkinson’s disease; mice; monocrotophos; oxidative stress; striatum; tyrosine hydroxylase