Impaired mitochondrial functions in organophosphate induced delayed neuropathy in rats.
Acute exposure to organophosphates induces a delayed neurodegenerative condition known as organophosphate-induced delayed neuropathy (OPIDN). The mechanism of OPIDN has not been fully understood as it does not involve cholinergic crisis. The present study has been designed to evaluate the role of mitochondrial dysfunctions in the development of OPIDN. OPIDN was induced in rats by administering acute dose of monocrotophos (MCP, 20 mg/kg body weight, orally) or dichlorvos (DDVP, 200 mg/kg body weight, subcutaneously), 15-20 min after treatment with antidotes [atropine (20 mg/kg body weight) and 2-PAM (100 mg/kg body weight) intraperitoneally]. MDA levels were observed to be higher and thiol content was lower in mitochondria from brain regions of OP exposed animals. This was accompanied by decreased activities of the mitochondrial enzymes; NADH dehydrogenase, succinate dehydrogenase, and cytochrome oxidase. In addition, mitochondrial functions assessed by MTT reduction also confirmed mitochondrial dysfunctions following development of OPIDN. The spatial long-term memory evaluated using elevated plus-maze test was observed to be deficit in OPIDN. The results suggest impaired mitochondrial functions as a mechanism involved in the development of organophosphate induced delayed neuropathy.
Masoud
Anwar
A
Department of Biochemistry, Basic Medical Science Building, Panjab University, Chandigarh, 160014, India.
Kiran
Ravi
R
Sandhir
Rajat
R
D000818:Animals; D004006:Dichlorvos / Q000008:administration & dosage / Q000633:toxicity; D004579:Electron Transport / Q000187:drug effects; D003576:Electron Transport Complex IV / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D009245:NADH Dehydrogenase / Q000378:metabolism; D009422:Nervous System Diseases / Q000139:chemically induced / Q000503:physiopathology*; D009483:Neuropsychological Tests; D010755:Organophosphates / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism
D010755:Organophosphates; D013438:Sulfhydryl Compounds; D008315:Malondialdehyde; D004006:Dichlorvos; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D005978:Glutathione