Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds.
Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin-induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur-containing compounds currently in clinical use may have equivalent or superior properties in this respect.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235.
Basinger
M A
MA
Holscher
M A
MA
D000818:Animals; D001710:Biotin / Q000627:therapeutic use; D001806:Blood Urea Nitrogen; D002216:Captopril / Q000627:therapeutic use; D002440:Cefoxitin / Q000627:therapeutic use; D002506:Cephalexin / Q000627:therapeutic use; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009929:Organ Size / Q000187:drug effects; D010400:Penicillin G / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013432:Sulfathiazoles / Q000627:therapeutic use; D013455:Sulfur / Q000627:therapeutic use*; D013831:Thiamine / Q000627:therapeutic use
D013432:Sulfathiazoles; D002440:Cefoxitin; D001710:Biotin; D013455:Sulfur; D002216:Captopril; D003404:Creatinine; D002506:Cephalexin; D002945:Cisplatin; D010400:Penicillin G; D013831:Thiamine