ABSTRACT
This chapter focuses on selected examples of key enzymes involved in the bioactivation of nephrotoxic chemicals and concentrates on some of the more recently described pathways. The renal bioactivation and nephrotoxicity of chloroform has been much studied and has been reviewed recently. Although normally safe in therapeutic doses, acute overdoses of acetaminophen are associated with hepatotoxicity, which is often accompanied by acute renal failure. A critical biochemical feature of its mechanism of nephrotoxicity is the active and selective accumulation of Cephaloridine in renal cortex by the organic anion transport system. The heme moiety of the peroxidase loses two electrons or gains oxygen during the reduction of peroxides. The chemicals that undergo bioactivation by this pathway include a variety of chemically unrelated compounds; many are halogenated alkanes or alkenes, as the halogen atom is a good leaving group in the nucleophilic addition of glutathione to the hydrocarbon.
