title: Protective efficacy of mitochondrial targeted antioxidant MitoQ against dichlorvos induced oxidative stress and cell death in rat brain.
abstract: Dichlorvos is a synthetic insecticide that belongs to the family of chemically related organophosphate (OP) pesticides. It can be released into the environment as a major degradation product of other OPs, such as trichlorfon, naled, and metrifonate. Dichlorvos exerts its toxic effects in humans and animals by inhibiting neural acetylcholinesterase. Chronic low-level exposure to dichlorvos has been shown to result in inhibition of the mitochondrial complex I and cytochrome oxidase in rat brain, resulting in generation of reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt c) from mitochondria to cytosol resulting in apoptotic cell death. MitoQ is an antioxidant, selectively targeted to mitochondria and protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in dichlorvos induced neurodegeneration, then MitoQ should ameliorate neuronal apoptosis. Administration of MitoQ (100 μmol/kg body wt/day) reduced dichlorvos (6 mg/kg body wt/day) induced oxidative stress (decreased ROS production, increased MnSOD activity and glutathione levels) with decreased lipid peroxidation, protein and DNA oxidation. In addition, MitoQ also suppressed DNA fragmentation, cyt c release and caspase-3 activity in dichlorvos treated rats compared to the control group. Further electron microscopic studies revealed that MitoQ attenuates dichlorvos induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that MitoQ may be beneficial against OP (dichlorvos) induced neurodegeneration.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
authors.forename: Willayat Yousuf
authors.initials: WY
authors.lastname: Wani
authors.forename: Satish
authors.initials: S
authors.lastname: Gudup
authors.forename: Aditya
authors.initials: A
authors.lastname: Sunkaria
authors.forename: Amanjit
authors.initials: A
authors.lastname: Bal
authors.forename: Parvinder Pal
authors.initials: PP
authors.lastname: Singh
authors.forename: Ramesh J L
authors.initials: RJ
authors.lastname: Kandimalla
authors.forename: Deep Raj
authors.initials: DR
authors.lastname: Sharma
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D053148:Caspase 3; D016923:Cell Death / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D004006:Dichlorvos / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D050050:Protein Carbonylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014451:Ubiquinone; C429014:mitoquinone; D004006:Dichlorvos; D045304:Cytochromes c; D013482:Superoxide Dismutase; D053148:Caspase 3