BIS (2, 3-dibromopropyl) phosphate nephrotoxicity

Effect of sex and CoCl2 pretreatment

W. Clayton Elliott, Jim Koski, Donald Houghton, Joan Hunter-Baines, William M. Bennett, R. K. Lynn

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1107-1117
Number of pages11
JournalLife Sciences
Volume32
Issue number10
DOIs
StatePublished - Mar 7 1983

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Rats
Phosphates
Toxicity
Metabolites
Metabolism
Enzyme inhibition
Kidney
Pharmaceutical Preparations
Creatinine
Serum

ASJC Scopus subject areas

  • Pharmacology

Cite this

Elliott, W. C., Koski, J., Houghton, D., Hunter-Baines, J., Bennett, W. M., & Lynn, R. K. (1983). BIS (2, 3-dibromopropyl) phosphate nephrotoxicity: Effect of sex and CoCl2 pretreatment. Life Sciences, 32(10), 1107-1117. https://doi.org/10.1016/0024-3205(83)90116-9

BIS (2, 3-dibromopropyl) phosphate nephrotoxicity : Effect of sex and CoCl2 pretreatment. / Elliott, W. Clayton; Koski, Jim; Houghton, Donald; Hunter-Baines, Joan; Bennett, William M.; Lynn, R. K.

In: Life Sciences, Vol. 32, No. 10, 07.03.1983, p. 1107-1117.

Research output: Contribution to journalArticle

Elliott, WC, Koski, J, Houghton, D, Hunter-Baines, J, Bennett, WM & Lynn, RK 1983, 'BIS (2, 3-dibromopropyl) phosphate nephrotoxicity: Effect of sex and CoCl2 pretreatment', Life Sciences, vol. 32, no. 10, pp. 1107-1117. https://doi.org/10.1016/0024-3205(83)90116-9
Elliott, W. Clayton ; Koski, Jim ; Houghton, Donald ; Hunter-Baines, Joan ; Bennett, William M. ; Lynn, R. K. / BIS (2, 3-dibromopropyl) phosphate nephrotoxicity : Effect of sex and CoCl2 pretreatment. In: Life Sciences. 1983 ; Vol. 32, No. 10. pp. 1107-1117.
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