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Sammanfattning

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.

Nyckelord

CYP1A1; CYP2E1; CYP3A; enzyme activity; organic solvent

Publicerad i

Toxicology Mechanisms and Methods
2015, volym: 25, nummer: 6, sidor: 501-506
Utgivare: TAYLOR & FRANCIS LTD

SLU författare

UKÄ forskningsämne

Farmakologi och toxikologi

Publikationens identifierare

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

Permanent länk till denna sida (URI)

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