Bis (2,3-dibromopropyl) phosphate nephrotoxicity: effect of sex and CoCl2 pretreatment.
Life Sci
; 32(10): 1107-17, 1983 Mar 07.
Article
em En
| MEDLINE
| ID: mdl-6827891
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Compostos Organofosforados
/
Organofosfatos
/
Cobalto
/
Rim
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1983
Tipo de documento:
Article