Pesticide induced muscle necrosis: mechanisms and prevention.
The nerve agent soman, as well as other organophosphates such as paraoxon and phospholine in concentrations that caused cholinergic symptoms induced a progressive dose-related necrosis in rat skeletal muscle fibers. The severity of the myopathy depended on a critical decrease in activity and duration of acetylcholinesterase (AChE) inhibition. The number of muscle fibers affected was greatest with soman, followed by tertiary phospholine, paraxon , and quaternary phospholine. The necrotic nerve fibers were repaired within 1 week. Atropine and gentamycin in concentrations that do not block neuromuscular transmission, attenuate the necrotic action of the organophosphates by interacting with the presynaptic Ca2+ uptake mechanism. The half-time recovery rate of AChE after exposure to soman varied between 12 hr for sciatic nerve, 5-9 days for muscle, and 14 days for brain. AChE activity of peripheral nerve was minimally inhibited by soman and had recovered to control activity within 24 hr. The reason for this apparent insensitivity of the nerve AChE to soman may be due to the high activity of an enzyme that hydrolyzes soman. AChE at the neuromuscular junction in part has a protective and regulatory function through its control of free acetylcholine (ACh). By limiting the accumulation of ACh and the extent of its interaction with pre- and postsynaptic membranes, the morphological integrity of nerve terminals and muscle is preserved.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors; D004456:Echothiophate Iodide / Q000633:toxicity; D005839:Gentamicins / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009135:Muscular Diseases / Q000139:chemically induced*; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012999:Soman / Q000633:toxicity; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
D002800:Cholinesterase Inhibitors; D005839:Gentamicins; D007306:Insecticides; D008345:Manganese; D001285:Atropine; D012999:Soman; D004456:Echothiophate Iodide; D000109:Acetylcholine