Thiol and thioether suppression of cis-platinum-induced nephrotoxicity in rats bearing the Walker 256 carcinosarcoma.
An examination of eighteen thiols and thio ethers revealed that the simultaneous administration of several of these with cis-platinum (CDDP) at 7.5 mg/kg (25 mumols/kg) iv, as a single injection to rats bearing the Walker 256 carcinosarcoma led to significant reduction in the nephrotoxicity typically found with cis-platinum, and no apparent interference in its anti-neoplastic action towards this tumor. The thiols and thiol ethers were administered at a twenty-fold molar excess to the CDDP and were combined with the CDDP immediately prior to administration. The most effective compounds in suppression nephrotoxicity were D-, and L-methionine, methyl and ethyl L-methioninate, and N-acetyl-D, L-methionine.
Jones
M M
MM
Department of Chemistry and Center in Molecular Toxicology, Vanderbilt University, Nashville, Tennessee 37235.
Basinger
M A
MA
D000818:Animals; D001806:Blood Urea Nitrogen; D002279:Carcinoma 256, Walker / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D004987:Ethers; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000627:therapeutic use*
D004987:Ethers; D013438:Sulfhydryl Compounds; D002945:Cisplatin