Monocrotophos toxicity and bioenergetics of muscle weakness in the rat.
Acute organophosphate pesticide poisoning is a common medical emergency with high fatality in agricultural communities of Asia. Organophosphate compounds inhibit acetylcholinesterase and prolonged neuromuscular weakness is a major cause of morbidity and mortality of poisoning. Organophosphate pesticide induced muscle weakness may not only arise from inhibition of acetylcholinesterase but also from non-cholinergic pathomechanisms, particularly mitochondrial dysfunction, affecting the production of sufficient ATP for muscle function. This study examined whether muscle weakness in rats subject to monocrotophos toxicity (0.8LD₅₀) was caused by inhibition of ATP synthesis, by oxidative phosphorylation and glycolysis, in addition to inhibition of muscle acetylcholinesterase. Severe muscle weakness in rats following monocrotophos administration was associated with inhibition of muscle acetylcholinesterase (30-60%) but not with reduced ATP production. The rats rapidly recovered muscle strength with no treatment. The ability of rats to spontaneously reactivate dimethoxy phosphorylated acetylcholinesterase and efficiently detoxify organophosphates may prevent severe inhibition of muscle acetylcholinesterase following acute severe monocrotophos poisoning. This may protect rodents against the development of prolonged muscle weakness induced by organophosphates.
Raghupathy
V
V
Wellcome Trust Research Laboratory, Department of Gastrointestinal Sciences, Christian Medical College, Vellore, India.
Poornima
S
S
Sivaguru
J
J
Ramachandran
A
A
Zachariah
A
A
Oommen
A
A
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D007306:Insecticides / Q000633:toxicity*; D008999:Monocrotophos / Q000633:toxicity*; D018908:Muscle Weakness / Q000139:chemically induced* / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D007306:Insecticides; D008999:Monocrotophos