Metabolic activation of nephrotoxic haloalkanes.
Worldwide industrialization and environmental pollution have increased the incidence of human exposure to halogenated aliphatic hydrocarbons, many of which are injurious to the mammalian kidney. Evaluation of human risk from haloalkane exposure requires knowledge about the mechanisms of the nephrotoxic effects of these agents so that appropriate animal models of human response can be developed. Recent studies indicate that nephropathy following methoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) anesthesia is caused by hepatic enzymatic release of inorganic fluoride ion, a nephrotoxic component of the parent molecule. Thus, the toxic effect is dependent upon hepatic metabolism of methoxyflurance. Acute chloroform injury to the kidney also may be caused by a toxic metabolite. In this case, however, the metabolite is most likely produced within the kidney. Chloride ion is relatively innocuous, suggesting that a carbon fragment of chloroform is the nephrotoxic agent. These results indicate that haloalkane metabolism, both renal and hepatic, can be important determinants of haloalkane nephropathy.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001711:Biotransformation; D002725:Chloroform / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000378:metabolism* / Q000633:toxicity; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced*; D008099:Liver / Q000378:metabolism; D008733:Methoxyflurane / Q000378:metabolism / Q000633:toxicity; D051381:Rats
D006846:Hydrocarbons, Halogenated; D008733:Methoxyflurane; D002725:Chloroform; D001189:Aryl Hydrocarbon Hydroxylases