TY - JOUR
T1 - Hepatic mixed function oxygenase activity and glutathione S-transferase activity in mice following ethanol consumption and withdrawal
AU - Schnellmann, Rick G.
AU - Wiersma, David A.
AU - Randall, Debra J.
AU - Smith, Thomas L.
AU - Sipes, I. Glenn
N1 - Funding Information:
*A preliminary report was presented at the 1983 Annual Conference of the Society of Toxicology, March, 1983, Las Vegas, Nevada. This work was supported by NIH grants ES-82130, ES-07091 and by the Research Service, Veterans Administration. The authors would like to acknowledge Haig Bozigian and Nancy Daly for their technical assistance and Pamela B. Murray for her assistance with manuscript preparation. **Present address: Dept. of Physiology, Duke University Medical Center, Box 3709-U, Durham, NC 27710, U.S.A. ***Address correspondence to: Dr. I. Glenn Sipes, Dept. Pharmacol./Toxicol., College of Pharmacy, University of Arizona, Tucson, AZ 85721, U.S.A. Abbreviations: BNZ, benzphetamine; BPH, biphenyl; BSA, bovine serum albumin; CDNB, 1-chloro-2,4-dinitrobenzene; DBE, 1,2-dibromethane; DMN, dimethyl-nitrosamine; DMSO, dimethyl sulfoxide; GSH, reduced glutathione; GST, glutathione S-transferase; G6P, glucose 6-phosphate; G6PDH, glucose-6-phosphate dehydrogenase; MFO, mixed function oxidase.
PY - 1984/8
Y1 - 1984/8
N2 - The effect of an 8 day liquid diet containing 7% v/v ethanol and the effect of ethanol withdrawal on several drug metabolizing enzyme activities, cytochrome P-450 content and glutathione S-transferase activity (GST) has been studied in male C57/BL mice. After treatment, hepatic microsomal activities toward benzphetamine (BNZ), biphenyl (BPH) and dimethylnitrosamine (DMN) and cytosolic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) were determined. Ethanol treatment caused a differential time dependent increase in the metabolism of the 4 xenobiotics. Increased BPH-4-hydroxylase activity correlated most closely with that of the increased concentration of hepatic P-450. That is, both values were increased (5.8-fold) over controls after 8 days of ethanol treatment. Ethanol withdrawal (24 h) resulted in a 46% reduction in the P-450 content and a 26% reduction in BPH-4-hydroxylase activity compared to the elevated values at day 8. By 48 h, the values were no different from controls. DNA-N-demethylase, BNZ-N-demethylase and GST activities all increased after 4 days of ethanol treatment and remained the same at 8 days. However, ethanol withdrawal resulted in differential time dependent changes in the activities towards BNZ, DMN, and CDNB. While DMN-N-demethylase activity returned to control activity within 24 h, BNZ-N-demethylase activity did not change for the first 24 h of withdrawal, but returned to control activity by 48 h. GST activity had not decreased by 48 h of withdrawal. These data suggest that ethanol induces several cytochrome P-450 isozymes that have a time difference in induction by ethanol and reduction following ethanol withdrawal. Furthermore, ethanol induction of GSTs occurs quickly (4 days) and remains elevated at least 48 h after ethanol withdrawal.
AB - The effect of an 8 day liquid diet containing 7% v/v ethanol and the effect of ethanol withdrawal on several drug metabolizing enzyme activities, cytochrome P-450 content and glutathione S-transferase activity (GST) has been studied in male C57/BL mice. After treatment, hepatic microsomal activities toward benzphetamine (BNZ), biphenyl (BPH) and dimethylnitrosamine (DMN) and cytosolic GST activity towards 1-chloro-2,4-dinitrobenzene (CDNB) were determined. Ethanol treatment caused a differential time dependent increase in the metabolism of the 4 xenobiotics. Increased BPH-4-hydroxylase activity correlated most closely with that of the increased concentration of hepatic P-450. That is, both values were increased (5.8-fold) over controls after 8 days of ethanol treatment. Ethanol withdrawal (24 h) resulted in a 46% reduction in the P-450 content and a 26% reduction in BPH-4-hydroxylase activity compared to the elevated values at day 8. By 48 h, the values were no different from controls. DNA-N-demethylase, BNZ-N-demethylase and GST activities all increased after 4 days of ethanol treatment and remained the same at 8 days. However, ethanol withdrawal resulted in differential time dependent changes in the activities towards BNZ, DMN, and CDNB. While DMN-N-demethylase activity returned to control activity within 24 h, BNZ-N-demethylase activity did not change for the first 24 h of withdrawal, but returned to control activity by 48 h. GST activity had not decreased by 48 h of withdrawal. These data suggest that ethanol induces several cytochrome P-450 isozymes that have a time difference in induction by ethanol and reduction following ethanol withdrawal. Furthermore, ethanol induction of GSTs occurs quickly (4 days) and remains elevated at least 48 h after ethanol withdrawal.
KW - Ethanol induction
KW - Ethanol withdrawal
KW - Glutathione S-transferase
KW - Mice
KW - Mixed function oxygenase
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U2 - 10.1016/0300-483X(84)90130-6
DO - 10.1016/0300-483X(84)90130-6
M3 - Article
C2 - 6540493
AN - SCOPUS:0021245371
SN - 0300-483X
VL - 32
SP - 105
EP - 116
JO - Toxicology
JF - Toxicology
IS - 2
ER -