Abstract

In vitro impacts of five organic solvents on cytochrome P450 (CYP450) enzyme activity were investigated using hepatic microsomes of rainbow trout. The rates of several CYP450-mediated reactions were investigated at solvent concentrations ranging from 0.01% to 3%. The solvents greatly affected all tested reactions. In at least 0.8% ethanol, 2% methanol or acetone, 1% acetonitrile or 3% dimethyl sulfoxide (DMSO), 7-ethoxyresorufin-O-deethylase (EROD) activity decreased and at 3% acetonitrile or ethanol, it was undetected. At 3%, all tested solvents except methanol reduced 7-benzyloxy-4-trifluoromethylcoumarin-O-debenzylase (BFCOD) activity, but at low concentrations of ethanol (2% and lower) or DMSO (1% and lower), it was induced. This was not seen with the inclusion of a pre-incubation step. p-Nitrophenolhydroxylase (PNPH) activity was not affected at concentrations below 1% DMSO, and at 2% acetonitrile it was reduced, as it was above 1% methanol or 0.5% ethanol. Acetone did not affect PNPH activity with or without a pre-incubation step. In general, the degree of inhibition was similar with and without the pre-incubation step. We conclude that the concentration of organic solvent for solubilizing the substrate and inhibitor in in vitro microsomal studies should be minimized.

Keywords

CYP1A1; CYP2E1; CYP3A; enzyme activity; organic solvent

Published in

Toxicology Mechanisms and Methods
2015, Volume: 25, number: 6, pages: 501-506 Publisher: TAYLOR & FRANCIS LTD

SLU Authors

• Zamaratskaia, Galia

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    
  • University of South Bohemia in České Budějovice

UKÄ Subject classification

Pharmacology and Toxicology


Publication identifier

DOI: https://doi.org/10.3109/15376516.2015.1074326

Permanent link to this page (URI)

https://res.slu.se/id/publ/75593