Defluorination: A possible mechanism of detoxification in rats exposed to fluoroacetate

An earlier study described a defluorinating system in the 105 000 × g supernatant fraction of rat liver which is stimulated in vitro by glutathione and inhibited by maleate. This work suggested the possible role of this defluorinating system in the detoxification of fluoroacetate in vivo. The current study reports the enhanced toxicity of fluoroacetate in animals in which liver glutathione has been depleted. Diethylmaleate pretreatment was found to reduce liver glutathione levels to 10% of control values 30 min after dosing. In animals pretreated with diethylmaleate the LD₅₀ of fluoroacetate was reduced by 35%. Increased toxicity of fluoroacetate with depletion of liver glutathione concentrations is consistent with a protective role for the glutathione requiring fluoroacetate defluorinating system in rat liver.