SYNERGISTIC INCREASES IN RAT HEPATIC CYTOCHROME P450S BY ETHANOL AND ISOPENTANOL

The purpose of this study was to determine if isopentanol alone or in combination with ethanol increased CYP2B1/2, CYP2E or CYP3A in the liv ers of rats. Increasing doses of isopentanol (0.5, 1, 2 or 3%) were ad ministered in combination with 5.6% ethanol in the Lieber-DeCarli liqu id diet for 7 days. Doses of 0.5 or 3% isopentanol were also administe red alone. Isopentanol alone caused small increases in CYP2B1/2 and CY P3A. However, when isopentanol (2 or 3%) was combined with ethanol a s ynergistic increase in P450281/2 was observed. The combined alcohol tr eatment also resulted in a greater increase in immunoreactive CYP3A th an either alcohol alone. Ethanol alone increased CYP2E 5-fold. Inclusi on of isopentanol with ethanol resulted in either small or no addition al increases in CYP2E. These results confirm our previous findings in cultured hepatocytes that when isopentanol is combined with ethanol, t here is a synergistic increase in CYP2B1/2. Increases in CYP2B1/2, CYP 2E and CYP3A protein moieties by ethanol, and by ethanol in combinatio n With isopentanol, were associated with increases in their mRNAs. Blo od isopentanol levels were 10-fold greater in rats administered 3% iso pentanol in combination with ethanol compared to rats administered 3% isopentanol alone. From these results we suggest that isopentanol, a h igher chain alcohol in alcoholic beverages, can contribute to increase s in hepatic cytochrome P450 observed following consumption of alcohol ic beverages.