Mitochondrial ATP synthase inhibition and nitric oxide are involved in muscle weakness that occurs in acute exposure of rats to monocrotophos.
Organophosphate poisoning in the context of self-harm is a common medical emergency in Asia. Prolonged muscle weakness is an important but poorly understood cause of morbidity and mortality of the poisoning. This study examined mitochondrial function and its modulation by nitric oxide in muscle weakness of rats exposed to an acute, oral (0.8LD(50)) dose of monocrotophos. Muscle mitochondrial ATP synthase activity was inhibited in the rat in acute exposure to monocrotophos while respiration per se was not affected. This was accompanied by decreased mitochondrial uptake of calcium and increased levels of nitric oxide. Reactive cysteine groups of ATP synthase subunits were reduced in number, which may contribute to decreased enzyme activity. The decrease in ATP synthase activity and reactive cysteine groups of ATP synthase subunits was prevented by treatment of animals with the nitric oxide synthase inhibitor, L-N(G) Nitroarginine methyl ester, at 12 mg/kg body weight for 9 days in drinking water, prior to monocrotophos exposure. This indicated a role for nitric oxide in the process. The alterations in mitochondrial calcium uptake may influence cytosolic calcium levels and contribute to muscle weakness of acute organophosphate exposure.
Venkatesh
S
S
Department of Neurological Sciences, Christian Medical College, Vellore, India.
Ramachandran
A
A
Zachariah
A
A
Oommen
A
A
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008931:Mitochondria, Muscle / Q000187:drug effects; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D008999:Monocrotophos / Q000633:toxicity*; D018908:Muscle Weakness / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009569:Nitric Oxide; D008999:Monocrotophos; D025261:Mitochondrial Proton-Translocating ATPases; D002118:Calcium