Histological and histochemical study of paraoxon myopathy in the rat

Time and dose dependency of paraoxon-induced myopathy in rats was studied in relation to esterase inhibition and clinical symptoms. High-dose poisoning resulted in a major cholinergic crisis with concomitant acetylcholinesterase inhibition in the first few hours with rapid restoration thereafter. Dose-dependent segmental muscle fiber necrosis occurred in clusters around the end-plates and was more frequent in diaphragms as compared to gastrocnemius muscles. However, in low-dose poisoned rats without major cholinergic symptoms or end-plate cholinesterase inhibition, necrotic fibers were also present. This indicates that not only end-plate cholinesterase inhibition but also neural or neuronal factors might be responsible for acetylcholine overflow and muscle fiber degeneration.