Bis (2,3-dibromopropyl) phosphate nephrotoxicity: effect of sex and CoCl2 pretreatment.
Bis (2,3-dibromopropyl) phosphate (BIS-BP) is one of two identified metabolites of Tris (2,3-dibromopropyl) phosphate (TRIS-BP). We have previously shown that BIS-BP is more acutely nephrotoxic than TRIS-BP. We now report the effect of sex and inhibition of drug metabolism on BIS-BP toxicity. Compared to male rats, age-matched female rats developed less severe and extensive structural damage after BIS-BP. Renal dysfunction, as indexed by serum creatinine and in vitro renal cortical uptake of para-aminohippurate and N-(14C) methylnicotinamide was similar in males and females. Pretreatment of males with the drug metabolism inhibitor, cobaltous chloride, reduced both functional and structural evidence of BIS-BP toxicity. In separate studies, there was no difference in the distribution of radiolabel in male and female rats three days after administration of 14C-TRIS-BP. These studies showing that female rats are resistant to acute BIS-BP structural damage may explain the previously reported lack of carcinogenicity of TRIS-BP in female rats. The reduction of BIS-BP toxicity by CoCl2 suggests that unidentified, nephrotoxic metabolites exist and are responsible for part of the nephrotoxicity of BIS-BP.
D000818:Animals; D003035:Cobalt / Q000494:pharmacology*; D003404:Creatinine / Q000097:blood; D004347:Drug Interactions; D005260:Female; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000473:pathology; D008297:Male; D009336:Necrosis; D010755:Organophosphates / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D051381:Rats; D012737:Sex Factors
D010755:Organophosphates; D009943:Organophosphorus Compounds; D003035:Cobalt; C035185:bis(2,3-dibromopropyl)phosphate; D003404:Creatinine; C018021:cobaltous chloride