Effect of arsenite on induction of CYP1A and CYP2H in primary cultures of chick hepatocytes

Toxicology and Applied Pharmacology
J M JacobsJ F Sinclair

Abstract

In earlier studies, treatment with sodium arsenite was shown to decrease total hepatic CYP in rats. A concomitant increase in heme oxygenase, the rate-limiting step in heme degradation to biliverdin, was considered responsible for the decrease in CYP. Here we investigated the effect of sodium arsenite on induction of CYP2H, CYP1A, and heme oxygenase in primary cultures of chicken embryo hepatocytes. When added simultaneously with inducer, arsenite inhibited phenobarbital-mediated increases in CYP2H and 3-methylcholanthrene-mediated increases in CYP1A, as measured enzymatically and immunochemically. Near maximal decreases were observed in these forms of CYP at a concentration of 2.5 microM sodium arsenite. The concentration-dependent decreases in CYP2H and CYP1A by sodium arsenite were concomitant with increases in heme oxygenase. Sodium arsenite was not toxic at concentrations as high as 10 microM, as indicated by protein synthesis and the reduction of MTT by intact cells. Sodium arsenite had no effect on induction of CYP2H1 mRNA, suggesting that the decreases in this form of CYP occurred post-transcriptionally. Treatment of cells with tin mesoporphyrin (SnMeso), an inhibitor of heme oxygenase, resulted in inhibition of arsenit...Continue Reading

References

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Citations

May 7, 2009·Expert Opinion on Drug Metabolism & Toxicology·Anwar Anwar-MohamedAyman Os El-Kadi
May 11, 2006·Drug Metabolism Reviews·Laurence Kaminsky
May 18, 1999·Toxicology and Applied Pharmacology·J M JacobsJ F Sinclair
Feb 2, 2013·Free Radical Biology & Medicine·Anwar Anwar-MohamedAyman O S El-Kadi
Apr 29, 2014·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·Patrick HeinrichThomas Braunbeck
Feb 13, 2001·Toxicology and Applied Pharmacology·D D VakhariaL S Kaminsky
Oct 24, 2000·Toxicology and Applied Pharmacology·J M JacobsJ F Sinclair
Apr 30, 2002·Journal of Biochemical and Molecular Toxicology·John M SeubertJohn R Bend
Feb 1, 2006·Archives of Environmental Contamination and Toxicology·N Suresh BabuV Ranganathan
Jan 24, 2007·The Journal of Biological Chemistry·Alex D SheftelPrem Ponka
Dec 14, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Anwar Anwar-MohamedAyman O S El-Kadi
Dec 4, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Erin E BessetteLaurence S Kaminsky
Oct 20, 1999·Archives of Biochemistry and Biophysics·J M JacobsJ F Sinclair
May 30, 2002·Mutation Research·Andrew MaierAlvaro Puga

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