title: Protection of dichlorvos induced oxidative stress and nigrostriatal neuronal death by chronic coenzyme Q10 pretreatment.
abstract: Numerous epidemiological studies have shown an association between pesticide exposure and increased risk of developing Parkinson's diseases. Oxidative stress generated as a result of mitochondrial dysfunction has been implicated as an important factor in the etiology of Parkinson's disease. Previously, we reported that chronic dichlorvos exposure causes mitochondrial impairments and nigrostriatal neuronal death in rats. The present study was designed to test whether Coenzyme Q(10) (CoQ(10)) administration has any neuroprotective effect against dichlorvos mediated nigrostriatal neuronal death, α-synuclein aggregation, and motor dysfunction. Male albino rats were administered dichlorvos by subcutaneous injection at a dose of 2.5 mg/kg body weight over a period of 12 weeks. Results obtained there after showed that dichlorvos exposure leads to enhanced mitochondrial ROS production, α-synuclein aggregation, decreased dopamine and its metabolite levels resulting in nigrostriatal neurodegeneration. Pretreatment by Coenzyme Q(10) (4.5 mg/kg ip for 12 weeks) to dichlorvos treated animals significantly attenuated the extent of nigrostriatal neuronal damage, in terms of decreased ROS production, increased dopamine and its metabolite levels, and restoration of motor dysfunction when compared to dichlorvos treated animals. Thus, the present study shows that Coenzyme Q(10) administration may attenuate dichlorvos induced nigrostriatal neurodegeneration, α-synuclein aggregation and motor dysfunction by virtue of its antioxidant action.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
authors.forename: B K
authors.initials: BK
authors.lastname: Binukumar
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004006:Dichlorvos / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D004006:Dichlorvos; C024989:coenzyme Q10