Effect of chloramphenicol pretreatment on malathion-induced acute toxicity in the rat

Pretreatment of rats with chloramphenicol (CAP) (100 mg/kg, ip) 30 min prior to a single oral LD50 dose of malathion (MTH) at 340 mg/kg completely protected against MTH-induced signs of cholinergic toxicity. Pretreatment with CAP also decreased the extent and duration of MTH-induced inhibition of cholinesterase (ChE). It was previously established that CAP inhibits (1) the cytochrome-P-450-catalyzed oxidative desulfuration of methylparathion to the much more toxic oxygen analog methylparaoxon (MOX) and (2) the carboxyesterase in rat liver. Since carboxyesterases account for 60% or more of the catabolism of MTH in the rat, the present results were surprising. Thus it appears that the inhibition of MTH toxicity by CAP pretreatment is attributable to inhibition by CAP of the metabolic activation of MTH to MOX.