Chemoprotection against cyclophosphamide-induced urotoxicity: ribose-cysteine.
2(R,S)-D-ribo-(1',2',3',4'-tetrahydroxybutyl) thiazolidine-4(R)-carboxylic acid (RibCys) is a prodrug of L-cysteine, which can facilitate the detoxication of numerous substances either directly or by providing the limiting amino acid for the biosynthesis of glutathione (GSH). RibCys was studied for its chemoprotective activity against the potent urotoxicity associated with the common anticancer agent, cyclophosphamide (CTX). In Swiss-Webster mice, RibCys given between 30 min before the toxin to 30 min after, either in a single or a split dose, exhibited powerful ability to protect against CTX-induced bladder inflammation and GSH depletion.
Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112.
J C
JC
Roberts
D J
DJ
Francetic
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000493:pharmacokinetics / Q000633:toxicity*; D003545:Cysteine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011355:Prodrugs / Q000378:metabolism / Q000494:pharmacology*; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*; D053778:Thiazolidines; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D011355:Prodrugs; D013844:Thiazoles; D053778:Thiazolidines; C070066:2-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4-carboxylic acid; D003520:Cyclophosphamide; D005978:Glutathione; D003545:Cysteine