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Heterogenic response of the liver parenchyma to ethanol studied in the bivascularly perfused rat liver

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Abstract

Zonation of ethanol oxidation and metabolic effects along the hepatic acini were investigated in the bivascularly perfused liver of fed rats. Ethanol was infused into the hepatic artery in antegrade and retrograde perfusion. Inhibition of glycolysis by ethanol, expressed as μmol min−1 (ml accessible cell space)−1, was more pronounced in the retrograde mode; the retrograde/antegrade ratio was equal to 1.63 for an ethanol infusion rate of 37.5 μmol min−1 g−1. Stimulation of oxygen uptake by ethanol was more pronounced in the retrograde mode; the retrograde/antegrade ratio was equal to 1.77. Diminution of the citrate cycle caused by ethanol was more pronounced in the retrograde mode; the retrograde/antegrade ratio was equal to 1.46. Transformation of arterially infused ethanol into acetate was more pronounced in retrograde perfusion; the retrograde/antegrade ratio was equal to 1.63. The increments in glucose release (glycogenolysis) caused by ethanol in the antegrade and retrograde modes were similar. It was assumed that the changes caused by arterially infused ethanol in retrograde and antegrade perfusion closely reflect a significant part of the periportal parenchyma and an average over the whole liver parenchyma, respectively. Under such assumptions it can be concluded that, in the perfused liver from fed rats, four related parameters predominate in the periportal region: ethanol oxidation, glycolysis inhibition, oxygen uptake stimulation and citrate cycle inhibition. One of the main causes for this predominance could be the malate/aspartate shuttle, which operates more rapidly in the periportal area and is essential for NADH oxidation.

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References

  1. Jungermann K, Katz R: Metabolic heterogeneity of liver parenchyma. In: H. Sies (ed). Metabolic Compartmentation. Academic Press, London, 1982, pp 411–435

    Google Scholar 

  2. Jungermann K, Thurman RG: Hepatocyte heterogeneity in the metabolism of carbohydrates. Enzyme 46: 33–58, 1992

    Google Scholar 

  3. Shiota M, Hiramatsu M, Fujimoto Y, Moriyama M, Kimura K, Ohta M, Sugano T: The capacity of the malate/aspartate shuttle differs between periportal and perivenous hepatocytes from rats. Arch Biochem Biophys 308: 349–356, 1994

    Google Scholar 

  4. Suzuki-Kemmelmeier F, Ishii-Iwamoto EL, Bracht A: The metabolism of fructose in the bivascularly perfused rat liver. Biochim Biophys Acta 1116: 275–282, 1992

    Google Scholar 

  5. Bracht A, Constantin J, Ishii-Iwamoto EL, Suzuki-Kemmelmeier F: Zonation of gluconeogenesis from lactate and pyruvate in the rat liver studied by means of anterograde and retrograde bivascular perfusion. Biochim Biophys Acta 1199: 298–304, 1994

    Google Scholar 

  6. Constantin J. Ishii-Iwamoto E, Suzuki-Kemmelmeier F, Bracht A: Zonation of the action of glucagon on gluconeogenesis studied in the bivascularly perfused rat liver. FEBS Lett 352: 24–26, 1994

    Google Scholar 

  7. Greenberger NJ, Cohen RB, Isselbacher KJ: The effect of chronic ethanol administration on liver alcohol dehydrogenase activity in the rat. Lab Invest 14: 264–271, 1965

    Google Scholar 

  8. Yamazaki H, Nishiguchi K, Inoue K, Yasuyama T, Nakanishi S: Intralobular distribution of rat liver aldehyde dehydrogenase and alcohol dehydrogenase. Int J Biochem 20: 435–437, 1988

    Google Scholar 

  9. Morrison GR, Brock FE: Quantitative measurement of alcohol dehydrogenase in the lobule of normal livers. J Lab Clin Med 70: 116–120, 1967

    Google Scholar 

  10. Yamauchi M, Potter JJ, Mezey E: Lobular distribution of alcohol dehydrogenase in the rat liver. Hepatology 8: 243–247, 1988

    Google Scholar 

  11. Kato S, Ishii H, Aiso S, Yamashita S, Ito D, Tsuchiya M: Histochemical and immunohistochemical evidence for hepatic zone 3 distribution of alcohol dehydrogenase in rats. Hepatology 12: 66–69, 1990

    Google Scholar 

  12. Maly IP, Sasse D: Intraacinar profiles of alcohol dehydrogenase and aldehyde dehydrogenase activities in human liver. Gastroenterology 101: 1716–1723, 1991

    Google Scholar 

  13. Kashiwagi T, Ji S, Lemasters JJ, Thurman RG: Rates of alcohol dehydrogenase-dependent ethanol metabolism in periportal and pericentral regions of the perfused rat liver. Mol Pharmacol 21: 438–443, 1981

    Google Scholar 

  14. Väänänen H, Lindros KO: Comparison of ethanol metabolism in isolated periportal or perivenous hepatocytes: Effects of chronic ethanol treatment. Alcohol Clin Exp Res 9: 315–321, 1985

    Google Scholar 

  15. Berry MN, Gregory RB, Grivell AR, Phillips JW, Schön A: The capacity of reducing-equivalent shuttles limits glycolysis during ethanol oxidation. Eur J Biochem 225: 557–564, 1994

    Google Scholar 

  16. Williamson JR, Scholz R, Browning ET, Thurman RG, Fukami MH: Metabolic effects of ethanol in perfused rat liver. J Biol Chem 244: 5044–5054, 1969

    Google Scholar 

  17. Thurman RG, Scholz R: Interaction of glycolysis and respiration in perfused liver. Changes in oxygen uptake following the addition of ethanol. Eur J Biochem 75: 13–21, 1977

    Google Scholar 

  18. Soboll S, Heldt HW, Scholz R: Changes in the subcellular distribution of metabolites due to ethanol oxidation in the perfused rat liver. Hoppe Seyler's Z Physiol Chem 362: 247–260, 1981

    Google Scholar 

  19. Häussinger D: Hepatocyte heterogeneity in glutamine and ammonia metabolism and the role of an intercellular glutamine cycle during ureogenesis in perfused rat liver. Eur J Biochem 133: 269–275, 1983

    Google Scholar 

  20. Häussinger D, Stehle T, Gerok W, Tran-Thi T, Decker K: Hepatocyte heterogeneity in response to extracellular ATP. Eur J Biochem 169: 645–650, 1987

    Google Scholar 

  21. Pang S, Cherry WF, Accaputo J, Schwab AJ, Goresky CA: Combined hepatic arterial-portal venous and hepatic arterial-hepatic venous perfusion to probe the abundance of drug metabolizing activities: Perihepatic venous O-deethylation activity for phenacetin and periportal sulfation activity for acetaminophen in the once-through rat liver preparation. J Pharmacol Exper Ther 247: 690–700, 1988

    Google Scholar 

  22. Pang KS, Sherman IA, Schwab AJ, Geng W, Barker F III, Dlugosz JA, Cuerrier G, Goresky CA: Role of the hepatic artery in the metabolism of phenacetin and acetaminophen: an intravital microscopic and multiple-indicator dilution study in perfused rat liver. Hepatology 20: 672–683, 1994

    Google Scholar 

  23. Fernandes TRL, Suzuki-Kemmelmeier F, Oliveira DS, Bracht A: Changes in distribution spaces and cell permeability caused by ATP in the rat liver. Liver 22: 35–42, 2002

    Google Scholar 

  24. Constantin J, Ishii-Iwamoto EL, Suzuki-Kemmelmeier F, Yamamoto N, Bracht A: The action of glucagon infused via the hepatic artery in anterograde and retrograde bivascular perfusion of the rat liver is not a function of the accessible cellular spaces. Biochim Biophys Acta 1244: 169–178, 1995

    Google Scholar 

  25. Clark LC: Monitoring and control of blood O2 tension. Trans Am Soc Artif Intern Organs 2: 41–49, 1956

    Google Scholar 

  26. Bergmeyer HU, Bernt E: Determination of glucose with glucose oxidase and peroxidase. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie-Academic Press, Weinheim-London, 1974, pp 1205–1215

    Google Scholar 

  27. Gutmann I, Wahlefeld AW: L-(+)-Lactate determination with lactate dehydrogenase and NAD. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie-Academic Press, Weinheim-London, 1974, pp 1464–1468

    Google Scholar 

  28. Czok R, Lamprecht W: Pyruvate, phosphoenolpyruvate and D-glycerate-2-phosphate. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie-Academic Press, Weinheim-London, 1974, pp 1446–1451

    Google Scholar 

  29. Bernt E, Gutmann I: Ethanol determination with alcohol dehydrogenase and NAD. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie-Academic Press, Weinheim-London, 1974, pp 1499–1502

    Google Scholar 

  30. Bernt E, Bergmeyer HU: Acetaldehyde. Determination with alcohol dehydrogenase from yeast. In: H.U. Bergmeyer (ed). Methods of Enzymatic Analysis. Verlag Chemie-Academic Press, Weinheim-London, 1974, pp 1506–1507

    Google Scholar 

  31. Scholz R, Olson MS, Schwab AJ, Schwabe U, Noell CH, Braun W: The effect of fatty acids on the regulation of pyruvate dehydrogenase in perfused rat liver. Eur J Biochem 86: 519–530, 1978

    Google Scholar 

  32. Morimoto Y, Wettstein M, Häussinger D: Hepatocyte heterogeneity in response to extracellular adenosine. Biochem J 293: 573–581, 1993

    Google Scholar 

  33. Fernandes TRL: Efeitos do ATP extracelular sobre a hemodinâmica e sobre a permeabilidade da membrana celular no fígado, University of Maringá, Maringá, Brazil, 2002

    Google Scholar 

  34. Oinonen T, Lindros KO: Zonation of hepatic cytochrome P-450 expression and regulation. Biochem J 329: 17–35, 1998

    Google Scholar 

  35. Wimmer M, Pette D: Microphotometric studies on intraacinar enzyme distribution in rat liver. Histochemistry 64: 23–33, 1979

    Google Scholar 

  36. Soboll S, Scholz R, Heldt HW: Subcellular metabolite concentrations. Dependence of mitochondrial and cytosolic ATP systems on the metabolic state of perfused rat liver. Eur J Biochem 87: 377–390, 1978

    Google Scholar 

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Lopez, C.H., Constantin, J., Gimenes, D. et al. Heterogenic response of the liver parenchyma to ethanol studied in the bivascularly perfused rat liver. Mol Cell Biochem 258, 155–162 (2004). https://doi.org/10.1023/B:MCBI.0000012850.90719.6e

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  • DOI: https://doi.org/10.1023/B:MCBI.0000012850.90719.6e

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