Comparison of ethanol metabolism in isolated periportal or perivenous hepatocytes: effects of chronic ethanol treatment.
Ethanol metabolism in rat hepatocytes isolated either from the periportal (pp) or the perivenous (pv) area by collagenase gradient perfusion was compared to reveal metabolic factors that could be associated with the development of perivenous alcoholic liver damage. Cells were also isolated from rats given ethanol (E) chronically by addition to the drinking fluid. One group (EM) received in addition the alcohol dehydrogenase inhibitor 4-methylpyrazole, which potentiated the ethanol treatment by causing sustained elevated diurnal blood ethanol levels. Fatty degeneration ensued in only one-third of the E rats but in all of the EM rats. The periportal/perivenous activity distributions of alanine aminotransferase (ALAT) and glutamate dehydrogenase (GLDH) were 2.2 and 0.75, respectively. Both ethanol treatments significantly decreased the ALAT and increased the GLDH activities, but did not change their pp/pv distributions. Ethanol treatment also increased ethanol and acetaldehyde oxidation, but to the same extent in pp and pv cells. The increase was more marked in cells from EM rats despite their more severe liver fatty degeneration. Ethanol incubation also increased the lactate/pyruvate ratio to the same extent in pp and pv cells both from control or ethanol-treated rats. Our results indicate that periportal and perivenous hepatocytes convert ethanol via acetaldehyde to acetate equally well and with similar effects even after chronic ethanol treatment. Consequently, preferential damage of the perivenous area after chronic ethanol intake is not caused by inherent or acquired differences in ethanol metabolism between perivenous and periportal hepatocytes. Rather, sinusoidal gradients only established in the intact liver may exaggerate the metabolic imbalance by ethanol in the perivenous area, thus explaining its greater vulnerability to damage by alcohol abuse.
D000079:Acetaldehyde / Q000378:metabolism; D000410:Alanine Transaminase / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D007773:Lactates; D011773:Pyruvates; D019344:Lactic Acid; D000431:Ethanol; D019289:Pyruvic Acid; D005969:Glutamate Dehydrogenase; D000410:Alanine Transaminase; D000079:Acetaldehyde