Mitochondrial oxidative stress and dysfunction in rat brain induced by carbofuran exposure.
Repeated low-dose exposure to carbofuran exerts its neurotoxic effects by non-cholinergic mechanisms. Emerging evidence indicates that oxidative stress plays an important role in carbofuran neurotoxicity after sub-chronic exposure. The purpose of the present study is to evaluate the role of mitochondrial oxidative stress and dysfunction as a primary event responsible for neurotoxic effects observed after sub-chronic carbofuran exposure. Carbofuran was administered to rats at a dose of 1 mg/kg orally for a period of 28 days. There was a significant inhibition in the activity of acetylcholinesterase (66.6%) in brain samples after 28 days of carbofuran exposure. Mitochondrial respiratory chain functions were assessed in terms of MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) reduction and activity of succinate dehydrogenase in isolated mitochondria. It was observed that carbofuran exposure significantly inhibited MTT reduction (31%) and succinate dehydrogenase activity (57%). This was accompanied by decrease in low-molecular weight thiols (66.6%) and total thiols (37.4%) and an increase in lipid peroxidation (43.7%) in the mitochondria isolated from carbofuran-exposed rat brain. The changes in mitochondrial oxidative stress and functions were associated with impaired cognitive and motor functions in the animals exposed to carbofuran as compared to the control animals. Based on these results, it is clear that carbofuran exerts its neurotoxicity by impairing mitochondrial functions leading to oxidative stress and neurobehavioral deficits.
Kamboj
Sukhdev Singh
SS
Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh 160014, India.
Kumar
Vikas
V
Kamboj
Amit
A
Sandhir
Rajat
R
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology*; D002235:Carbofuran / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D003072:Cognition Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000503:physiopathology; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000032:analysis / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013778:Tetrazolium Salts
D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D013438:Sulfhydryl Compounds; D013778:Tetrazolium Salts; D013385:Succinate Dehydrogenase; D000110:Acetylcholinesterase; D002235:Carbofuran