Thioether suppression of cisplatin nephrotoxicity in the rat.
Six compounds containing a thioether group were examined as agents for the reduction of the nephrotoxicity caused by cisplatin (CDDP) in the rat. Of these, five were able to reduce the CDDP- induced nephrotoxicity when administered simultaneously with CDDP (8.0 mg/kg, iv). The compounds capable of reducing CDDP toxicity were L-methioninamide, cystathionine, methionyl-L-alanine, (methythio) acetic acid and 4-(methylthio) benzoic acid. Indices used to evaluate toxicity included body weight changes, BUN and serum creatinine levels and the histopathological examination of renal tissue. The platinum levels of renal tissue were determined but were found not to correlate well with other measures of renal function. Oral administration of the more effective of these compounds was found to provide a reduced level of protection against the nephrotoxicity caused by iv CDDP. The most effective of these compounds caused a very modest reduction in the anti-tumor activity of CDDP as measured against the L1210 murine leukemia.
Jones
M M
MM
Department of Chemistry, Vanderbilt University, Nashville Tennessee 37235.
Basinger
M A
MA
Holscher
M A
MA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D003540:Cystathionine / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000494:pharmacology*
D013440:Sulfides; D003540:Cystathionine; D008715:Methionine; D002945:Cisplatin; C018594:methioninamide