Decreased incidence of diphenylamine-induced renal papillary necrosis in Syrian hamsters given dimethylsulphoxide.
The renal papillotoxicity of diphenylamine dissolved in dimethylsulphoxide (DMSO) was investigated in male Syrian hamsters, male Sprague-Dawley rats and female Mongolian gerbils. When diphenylamine in DMSO was administered orally to male Syrian hamsters (400, 600 or 800 mg/kg body weight/day for up to 9 days), the incidence of renal papillary necrosis was almost zero. Hamsters pretreated with DMSO (0.5 ml/100 g body weight/day) and 1 hr later given 400, 600 or 800 mg diphenylamine in peanut oil/kg body weight/day for 3 consecutive days had significantly reduced incidences of renal papillary necrosis (0/10, 0/10 and 1/10 in the low-, mid- and high-dose groups, respectively) when compared with hamsters given similar doses of diphenylamine but not pretreated with DMSO (5/10, 7/10 and 5/10 in the low-, mid- and high-dose groups, respectively). Focal, apex-limited renal papillary necrosis was observed in two Sprague-Dawley rats given 800 mg diphenylamine in DMSO/kg body weight/day orally for 9 days. Focal, intermediate renal papillary necrosis was observed in two additional rats administered 800 mg diphenylamine in DMSO/kg/day orally for 9 days. Renal papillary necrosis was not observed in any of the Mongolian gerbils. The results of these studies suggest that DMSO protects against diphenylamine-induced renal papillary necrosis in male Syrian hamsters.
Lenz
S D
SD
Department of Veterinary Pathobiology, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47906.
Carlton
W W
WW
D000284:Administration, Oral; D000818:Animals; D006224:Cricetinae; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000627:therapeutic use*; D004159:Diphenylamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005849:Gerbillinae; D007274:Injections, Intraperitoneal; D007672:Kidney Cortex / Q000187:drug effects / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008647:Mesocricetus; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D004159:Diphenylamine; D004121:Dimethyl Sulfoxide