Time course for the elevation of glutathione in numerous organs of L1210-bearing CDF1 mice given the L-cysteine prodrug, RibCys.
RibCys, a thiazolidine prodrug of L-cysteine synthesized by the condensation of the sulfhydryl-containing amino acid with the aldose monosaccharide D-ribose, successfully elevated glutathione (GSH) levels in numerous organs of tumor-bearing CDF1 mice. GSH content was assayed 1,2,4,8 and 16 h after RibCys administration (8 mmol/kg, i.p.); various organs achieved maximal GSH content at different time points. GSH in the liver was elevated 1.5-fold compared to untreated controls at the 16-h time point. Kidney GSH also was maximal at 16 h and achieved 1.6-times control values. GSH in muscle achieved 2.5 times the levels in control animals, while the bladder was elevated 2.1-fold, and the heart 1.8-fold. Other tissues tested (spleen, pancreas, lung) showed a 1.1- to 1.2-fold increase in GSH content. GSH in implanted L1210 tumors was also elevated only 1.2-fold. These data suggest the possibility of protecting organs other than the liver from toxic insults that require the intervention of GSH for detoxication and may allow such protection without compromising the utility of chemotherapy.
Roberts
J C
JC
Department of Medicinal Chemistry, University of Utah, Salt Lake City 84112.
Francetic
D J
DJ
D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives; D005978:Glutathione / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D011355:Prodrugs / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D053778:Thiazolidines
D011355:Prodrugs; D013844:Thiazoles; D053778:Thiazolidines; C070066:2-(1',2',3',4'-tetrahydroxybutyl)thiazolidine-4-carboxylic acid; D005978:Glutathione; D003545:Cysteine