Genetically Mediated Responses of Microsomal Ethanol Oxidation in Mice
Long-sleep (LS) and Short-sleep (SS) male mice were treated chronically with alcohol for 30 days. Ethanol treated mice were withdrawn from alcohol diet at 8, 12, 16, 20, 24 and 30 days of treatment for the assessment of metabolic tolerance and numerous parameters associated with the microsomal cytochrome P-450 complex. Up to 20 days of ethanol treatment, LS and SS mice displayed nearly the same enhancement of in vivo ethanol elimination rates. At 24 and 30 days of ethanol treatment, LS mice were found to have significantly greater ethanol elimination rates than SS mice chronically treated with alcohol. The induction of microsomal cytochrome P-450 content and microsomal ethanol oxidation paralleled the acquisition of metabolic tolerance with LS mice displaying significantly greater values of both microsomal parameters at 24 and 30 days of treatment. Aniline hydroxylase was maximally induced (2.5 fold) in both LS and SS mice by 16 days of treatment. Chronic ethanol treatment resulted in a significant induction of ethylmorphine and benzphetamine N-demethylase activity in both LS and SS mice with the SS selected line showing a greater (P<.05) maximal induction. These data are suggestive that the induction of MEOS may have some significance in the acquisition of metabolic tolerance to ethanol and that there may be a genetic predisposition for these adaptive responses.
KeywordsChronic Ethanol Ethanol Treatment Ethanol Administration Chronic Alcohol Ingestion Aniline Hydroxylase
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- Chung, L. W. K., Raymond, G. and Fox, S., 1975, Role of neonatal androgen in the development of hepatic microsomal drug metabolizing enzymes, J. Pharmacol. Exp. Ther., 146: 225.Google Scholar
- DeCarli, L. M. and Lieber, C. S., 1967, Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet, J. Nutr., 91: 331.Google Scholar
- Gornall, A. G., Bardawill, C. J. and David, M. M., 1949, Determination of serum proteins by means of the biuret reaction, J. Biol. Chem., 247: 1125.Google Scholar
- Ioannides, C. and Parke, D. V., 1973, The effect of ethanol administration on drug oxidations and possible mechanisms of ethanol-barbiturate interactions, Biochem. Soc. Trans., 1: 716.Google Scholar
- Joly, J. G., Ishii, H., Teschke, R., Hasumura, Y. and Lieber, C. S., 1973, Effect of chronic ethanol feeding on the activities and submicrosomal distribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome P-450 reductase and the demethylases for aminopyrene and ethylmorphine, Biochem. Pharmacol., 22: 1532.PubMedCrossRefGoogle Scholar
- Lieber, C. S. and DeCarli, L. M., 1972, The role of the hepatic microsomal ethanol oxidizing system ( MEOS) for ethanol metabolism in vivo, J. Pharmacol. Exp. Therap., 181: 279.Google Scholar
- McClearn, G. E., Wilson, J. R. and Meredity, W., 1970, Contributions to Behavior-Genetic Analysis: The Mouse As A PrototypeGoogle Scholar
- G. Lindzey, G. G. Lindsey and D. D. Thiessen, eds., Appleton-Century Crofts, New York.Google Scholar
- Misra, P. S., Lefevre, A., Ishii, H., Rubin, E. and Lieber, C. S., 1971, Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and rats, Am. J. Med., 18: 227.Google Scholar
- Thurman, R. G., McKenna, W. R., Brentzel, H. J. and Hesse, S, 1975, Significant pathways of hepatic ethanol metabolism, Fed. Proc., 34: 11.Google Scholar