Abstract
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 (0.8LD50) 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-NG 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.
Highlights
Organophosphorous pesticide poisoning is a common method of intentional self-harm in agricultural communities across Asia (Eddleston and Phillips 2004)
RBC AChE levels in control rats were 8.96 ± 0.456 units/mg protein that decreased to 0.253 ± 0.218 units/mg protein in monocrotophos treated animals
All rats treated with monocrotophos exhibited cholinergic symptoms and muscle weakness
Summary
Organophosphorous pesticide poisoning is a common method of intentional self-harm in agricultural communities across Asia (Eddleston and Phillips 2004). Organophosphates inhibit acetylcholinsterase (AChE), leading to an accumulation of acetylcholine at cholinergic synapses in the central nervous system and at neuromuscular junctions, and that results in overstimulation of these systems. This can result in an autonomic cholinergic storm and lead to prolonged neuromuscular weakness and paralysis. The pathophysiology underlying muscle weakness that occurs in acute OPP is not completely clear, and there is no specific treatment for it. It is a major cause of morbidity and mortality of hospitalized OPP patients (Samuel et al 1995). Persistent inhibition of AChE is the primary event responsible for muscle weakness that occurs in OPP
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