Inhibition of rat renal C-S lyase: assessment using kidney slice methodology

Renal C-S lyase enzymes are implicated in the biotransformation of xenobiotics into potentially toxic metabolites by a deviation from the normal pathways of glutathione conjugate processing. C-S lyase enzymes occur in gastro-intestinal bacteria, and in liver as well as in mammalian and avian kidney. The renal enzyme cleaves the carbon-sulphur bond in cysteine conjugates derived from halogenated olefins (e.g. tetrafluoroethene, trichloroethene, and hexachlorobutadiene). Substituted S-nitrophenyl conjugates, which are analogues of a substrate for the hepatic C-S lyase enzyme (S-2,4-dinitrophenyl-L-cysteine), are demonstrated to display significant inhibition of rat renal C-S lyase using kidney slice methodology. They are also shown to disrupt the tubular uptake of organic cations and anions.