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.
Blagbrough
I S
IS
Department of Pharmaceutical Sciences, University of Nottingham, School of Pharmacy, University Park.
Bycroft
B W
BW
Evans
D C
DC
Shaw
P N
PN
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D002412:Cations / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003600:Cytosol / Q000201:enzymology; D003640:Dealkylation; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D007672:Kidney Cortex / Q000201:enzymology; D008190:Lyases / Q000037:antagonists & inhibitors*; D008297:Male; D011773:Pyruvates / Q000378:metabolism; D051381:Rats
D002412:Cations; D011773:Pyruvates; D000641:Ammonia; D008190:Lyases; C033511:carbon-sulfur lyase; D003545:Cysteine