Indium selectively increases the cytochrome P-450 dependent O-dealkylation of coumarin derivatives in male mice

Naunyn-Schmiedeberg's Archives of Pharmacology
S A MangouraK J Netter

Abstract

Indium pretreatment of rats and mice has been reported to decrease the concentration of cytochrome P-450, thereby reducing the activity of some cytochrome P-450 dependent enzymatic reactions. The present study reveals that pretreatment of C57Bl/6JHan mice of both sexes with one s.c. dose of 120 mg of In2(SO4)3.5 H2O per kg of body weight decreases the concentration of cytochrome P-450 to about 65% of control levels. Neither cytochrome b5 nor NADPH-cytochrome P-450 reductase is affected. Hepatic microsomal ethoxyresorufin O-deethylase activity declines to about 75% of control values. In contrast, with coumarin substrates, a sex dependence in the direction of change is observed: in female mice indium decreases the activity to about 75%, whereas in males it enhances the activity to 140%. Moreover, with 7-(methoxy-14C)coumarin as substrate, indium-pretreated male mice exhale about 180% and females about 65% of 14CO2 compared to the corresponding controls. A close correlation between the in vivo and in vitro effects of indium on the metabolism of the coumarin derivatives is suggested. After isolation and purification of cytochrome P-450, SDS-PAGE indicates in indium-pretreated male mice an intensification of a 48.5 kDa protein band ...Continue Reading

References

Jul 1, 1979·Toxicology and Applied Pharmacology·J S WoodsB A Fowler
Apr 1, 1978·Analytical Biochemistry·A Aitio
Apr 1, 1979·Toxicology and Applied Pharmacology·W LegrumK J Netter
Oct 1, 1985·European Journal of Biochemistry·R O JuvonenM A Lang
Dec 1, 1968·Japanese Journal of Pharmacology·R KatoM Takayanagi
Dec 1, 1983·Archives of Toxicology·D Lorke

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Citations

Aug 1, 1993·Biological Trace Element Research·M IşcanM Işcan
Jun 1, 1990·Trends in Neurosciences·H R Guy, F Conti
Nov 1, 1994·European Journal of Pharmacology·P PellinenM Pasanen
Sep 27, 2005·Biochemical Pharmacology·A'edah Abu-BakarMatti A Lang

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