Effects of chronic paraoxon administration on skeletal muscle fiber integrity

Rats were injected daily for up to 60 days with low doses of paraoxon to determine the effects of chronic organophosphate cholinesterase (ChE) inhibition on skeletal muscle fiber integrity. Administration of .05 or .10 mg/kg paraoxon for 30 days did not lead to any overt signs of organophosphate toxicity, but did produce lesions in diaphragm muscle. Further injections, for up to 60 days, did not increase the severity of the myopathy. ChE activity in the end plate region of the diaphragm was progressively inhibited by both doses of paraoxon throughout the 60 day period. Enzyme activity in the non-end plate region from rats injected with .05 mg/kg was unaffected until 60 days of injections, while activity in muscle from rats receiving the higher dose was maximally inhibited after 15 days and remained at that level of inhibition for the remaining 45 days. Plasma ChE activity was maximally inhibited by both doses at 15 days of injection. Acetylcholinesterase (AChE) activity in red blood cells from rats injected with the low dose of paraoxon showed a progressive inhibition throughout the treatment schedule, whereas enzyme activity in red blood cells from rats receiving the higher dose was maximally inhibited by 15 days. Results indicate that prolonged exposure to low doses of organophosphate ChE inhibitors leads to necrosis of skeletal muscle fibers and may be observed without other overt signs of organophosphate toxicity.