Major role of cytochrome P450 2E1 in ethanol oxidation by Kupffer cells

To examine ethanol oxidation by cultured rat Kupffer cells, we measured [¹⁴C]-acetate formation from [¹⁴C]-ethanol. Diallyl sulfide (1 mM), and miconazole (60 μ M), respectively inhibitors of cytochrome P450 2E1 and NADPH cytochrome P450 reductase, significantly attenuated acetate formation from 20 mM or 50 mM ethanol. Sodium azide (1 mM), an inhibitor of catalase, significantly suppressed acetate formation from 50 mM ethanol and tended to suppress it at 20 mM. However, 4-methylpyrazole (2 mM), an inhibitor of class I alcohol dehydrogenase, failed to suppress ethanol oxidation at either concentration. A reverse-transcription polymerase chain reaction demonstrated that Kupffer cells carry mRNAs for cytochrome P450 2E1 and catalase, but not for class I alcohol dehydrogenase. It can thus be argued that cytochrome P450 2E1 plays a major role in ethanol oxidation by Kupffer cells.