Abstract
We have demonstrated that in rats subjected topartial hepatectomy (PH), the regenerating liver had anenhanced metabolism of ethanol, which largely dependedon the route and timing of ethanol administration. Therefore, the influence of the administrationroute and timing for ethanol-induced deleterious effectson the regenerating rat liver was evaluated in animalssubjected to 70% PH. Remnant liver showed moderate fatty infiltration, extended distortion ofhepatocellular structure, and high mitotic index.Intragastric ethanol administration (1.5 g/kg bodyweight) considerably reduced the PH-induced changes inliver structures. Ethanol treatment also decreasedliver thymidine kinase activity, serum albumin, andglucose levels. Intraperitoneal administration of thesame ethanol dose to PH rats promoted lesser alterations on liver regeneration. Independently of itsadministration route, ethanol abruptly shortened aPH-induced selective increase in serum enzymeactivities. These data suggest that the inhibitoryeffect of a low dose of ethanol on PH-induced liverregeneration is dependent on the timing and route ofadministration.
Similar content being viewed by others
REFERENCES
Nakata R, Tsukamoto I, Nanme M, Makino S, Miyoshi M, Kojo S: Alfa adrenergic regulation of the activity of thymidylate synthetase and thymidinekinase during liver regeneration after partial hepatectomy. Eur J Pharmacol 114:355–360, 1985
Scornik OA, Botbol V: Role of changes in protein degradation in the growth of regenerating livers. J Biol Chem 251:2891, 1976
Scornik OA: In vivo rate of translation by ribosomes and regenerating liver. J Biol Chem 249:3876, 1974
Higgins ES, Banks WL: Cognate effects of ethanol, hydrazine and tissue regeneration on hepatic mitochondrial activities. Biochem Pharmacol 20:1513, 1976
Fausto N, Butcher FR: Cyclic nucleotide levels in regenerating liver. Biochim Biophys Acta 428:702, 1976
Wands JR, Carter EA, Bucher NLR, Isselbacher KJ: Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication. Gastroenterology 77:528–531, 1979
Frank WO, Rayyes AN, Washington A, Holt PR: Effect of acute ethanol administration upon hepatic regeneration. J Lab Clin Med 93:402–413, 1979
Pösö AR, Pösö H: Inhibition of ornithine decarboxylase in regenerating rat liver by acute athanol treatment. Biochim Biophys Acta 606:338–346, 1980
Pösö H, Pösö AR: Inhibition of RNA and protein synthesis by ethanol in regenerating rat liver: evidence for transcriptional inhibition of protein synthesis. Acta Pharmacol Toxicol 49:125–129, 1981
Yoshida Y, Komatsu M, Ozeki A, Nango R, Tsukamoto I: Ethanol represses thymidylate synthase and thymidinekinase at mRNA level in regenerating rat liver after partial hepatectomy. Biochim Biophys Acta 1336:180–186, 1997
Dugay L, Coutu D, Hetu C, Joly JG: Inhibition of liver regeneration by chronic alcohol administration. Gut 23:8–13, 1982
Morales-González JA, Gutiérrez-Salinas J, Hernández-Muñoz R: Pharmacokinetics of the ethanol bioavailability in the regenerating rat liver induced by partial hepatectomy. Alcohol Clin Exp Res 22:1557–1563, 1998
Higgins GM, Anderson RM: Experimental pathology of the liver: restoration of the liver of the white rat following partial surgical removal. Arch Pathol 12:186–202, 1931
Aguilar-Delfón I, López-Barrera F, Hernández-Muñoz R: Selective enhancement of lipid peroxidation in plasma membrane in two experimental models of liver regeneration: partial hepatectomy and acute CCI4 administration. Hepatology 24:657–662, 1996
Niemela O, Parkkila S, Ylä-Herttuala S, Villanueva J, Ruebner B, Halsted CH: Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcoholinduced liver disease. Hepatology 22:1208–1214, 1995
Horder M, Rej R: Alanine aminotransfe rase (glutamate pyruvate transaminase ) In Methods of Enzymatic Analysis. HU Bergmeyer, J Bergmeyer, M Grassl (eds). Deerfield Beach, Florida, Verlag Chemie, 1983, pp 444–450
Hernández-Muñoz R, Díaz-Muñoz M, Suárez J, Chagoya de Sánchez V: Adenosine partially prevents cirrhosis induced by carbon tetrachloride in rats. Hepatology 12:242–248, 1990
Vassault A: Lactate dehydrogenase. UV-method with pyruvate and NADH. In Methods of Enzymatic Analysis. HU Bergmeyer, J Bergmeyer, M Grassl (eds). Deerfield Beach, Florida, Verlag Chemie, 1983, pp 118–126
Ceriotti G: Ornithine carbamoyl transferase. In Methods of Enzymatic Analysis. HU Bergmeyer, J Bergmeyer, M Grassl (eds).Deerfield Beach, Florida, Verlag Chemie, 1983, pp 319–332
Ellis G, Goldberg DM: Optimal conditions for the kinetic assay of serum glutamate dehydrogenase activity at 37°C. Clin Chem 18:523–527, 1972
Sauer H, Wilmanns W: Thymidine kinase. In Methods of Enzymatic Analysis. HU Bergmeyer, J Bergmeyer, M Grassl (eds). Deerfield Beach, Florida, Verlag Chemie, 1983, pp 468–473
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275, 1951
Jordan SW: Electron microscopy of hepatic regeneration. Exp Mol Pathol 3:183–200, 1964
Trotter NL: A fine structure study of lipid in mouse liver regenerating after partial hepatectomy. J Cell Biol 21:233–244, 1964
Lane BP, Becker FF: Regeneration of the mammalian liver. II. Surface alterations during dedifferentiation of the liver cell in preparation for cell division. Am J Pathol 48:183–196, 1966
Aterman K: Electron microscopy of the rat liver cell after partial hepatectomy. J Pathol Bacteriol 82:367–369, 1961
Fisher ER, Fisher B: Ultrastructural hepatic changes following partial hepatectomy and portacaval shunt in the rat. Lab Invest 12:929–942, 1963
Tsukamoto I, Taniguchi Y, Miyoshi M, Kojo S: Purification and characterization of thymidine kinase from regenerating rat liver. Biochim Biophys Acta 1079:348–352, 1991
Jikko A, Taki Y, Nakamura N, Tanaka J, Kamiyama Y, Ozawa K, Tobe T: Adenylate energy charge and cytochrome a ( +a 3) in the cirrhotic rat liver. J Surg Res 37:361–368, 1984
Gutiérrez-Salinas J, Aranda-Fraustro A, Paredes-Díaz R, Hernandez-Muñoz R: Sucrose administration to partially hepatectomized rats: A possible model to study ethanol-induced inhibition of liver regeneration. Int J Biochem Cell Biol 28:1007–1016, 1996
Hernández-Muñoz R, Santamaría A, García-Sáinz JA, Piña E, Chagoya de Sánchez V: On the mechanism of ethanol-induced fatty liver and its reversibility by adenosine. Arch Biochem Biophys 190:155–162, 1978
Morsiani E, Mazzoni M, Aleotti A, Gorini P, Ricci D: Increased sinusoidal wall permeability and liver fatty change after two-third hepatectomy: An ultrastructural study in the rat. Hepatology 21:539–544, 1995
Frederiks WM, Vogels IM, Fronik GM: Plasma ornithine carbamyl transferase level as an indicator of ischaemic injury of rat liver. Cell Biochem Funct 2:217–220, 1984
Van Waes L, Lieber CS: Glutamate dehydrogenase: A reliable marker of liver cell necrosis in the alcoholic. Bri J Med 2:1508–1510, 1977
Sato T, Tanaka J, Kono Y, Jones RT, Cowley RA, Trump BF: Hepatic cellular injury following lethal bacteremia in rats. Lab Invest 47:304–310, 1982
Menache R, Feller N, Halbrecht I, Djaldetti M: Enzyme activities in regenerating liver of rats. Res Exp Med (Berl) 177:53–55, 1980
Kim S, Cohen PP: Transcarbamylase activity in fetal liver and in liver of partially hepatectomized parabiotic rats. Arch Biochem Biophys 109:421–428, 1965
Bengmark S, Engevik L, Olsson R: Changes in ornithine carbamyl transferase activity in serum and in liver after partial hepatectomy in rats. Scand J Gastroenterol 3:264–266, 1968
Sekas G, Cook RT: The evaluation of liver function after partial hepatectomy in the rat: Serum changes. Br J Exp Pathol 60:447–452, 1979
Zimmerman HJ: Serum enzyme measurement. In International Symposium on Hepatotoxicity, M. Eliakem, J. Eschchar, HJ Zimmerman (eds). New York, Academic Press, 1974, pp 315–323
Dinman BD, Bernstein IA: Acute carbon tetrachloride hepatotoxicity. Enzymatic activity and structural concomitants during the regenerative phase. Arch Environ Health 16:777–786, 1968
Lieber CS, Rubin E: Alcoholic fatty liver. N Engl J Med 280:705–708, 1969
Rights and permissions
About this article
Cite this article
Morales-Gonzalez, J.A., Gutierrez-Salinas, J., Yanez, L. et al. Morphological and Biochemical Effects of a Low Ethanol Dose on Rat Liver Regeneration Role of Route and Timing of Administration. Dig Dis Sci 44, 1963–1974 (1999). https://doi.org/10.1023/A:1026601814082
Issue Date:
DOI: https://doi.org/10.1023/A:1026601814082