Protective effect of sodium-2-mercaptoethanesulfonate on the gastrointestinal toxicity and lethality of cis-diamminedichloroplatinum.
cis-Diamminedichloroplatinum (cis-platinum) is an effective and widely used antitumor drug. Patients receiving cis-platinum, however, experience very profound and long lasting gastrointestinal symptoms. The role of intestinal mucosal toxicity in the pathogenesis of these symptoms is unclear. In this study we have investigated the thiol-containing compound mesna (sodium-2-mercaptoethanesulfonate) as a potential antidote to cis-platinum-induced gastrointestinal tract damage. In mice, mesna caused a significant reduction in the gastrointestinal toxicity of cis-platinum assessed by electron microscopy, villus recovery rate, and by disaccharidase estimations. Mesna also significantly reduced serum creatinine levels following cis-platinum. Administration of mesna prior (or immediately following) a 67% lethal dose of cis-platinum protected 87-100% of the animals from the lethal effects. The antitumor efficacy of cis-platinum in L1210 leukemia bearing mice was not affected by coadministration of mesna indicating that the protective effect may be tissue specific. In addition this finding indicates that mesna has potential as an agent which may improve the therapeutic index of cis-platinum in clinical practice.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D004186:Disaccharidases / Q000378:metabolism; D004334:Drug Administration Schedule; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D008623:Mercaptoethanol / Q000031:analogs & derivatives*; D015080:Mesna / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008855:Microscopy, Electron, Scanning
D008623:Mercaptoethanol; D004186:Disaccharidases; D015080:Mesna; D002945:Cisplatin