PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of gutGutView this articleSubmit a manuscriptReceive email alertsContact usBMJ
 
Gut. 1982 January; 23(1): 8–13.
PMCID: PMC1419599

Inhibition of liver regeneration by chronic alcohol administration.

Abstract

Liver regeneration is the common mechanism whereby a patient recovers form a liver injury. In the western world, ethanol is the single most important aetiological factor associated with liver disease, and it appears crucial to determine if ethanol interferes with liver regeneration. We studied the response to a 70% hepatectomy in 240 rats receiving a nutritionally adequate diet containing 36% of their calories as ethanol for three weeks and their pair-fed controls receiving a liquid diet where ethanol is isocalorically replace with carbohydrates. Criteria of liver regeneration were: incorporation of 3H-thymidine in hepatocyte DNA (cpm/10 microgram DNA) and number of hepatocyte labelled nuclei on autoradiography per 100 high power fields. Controls displayed the usual response with peak activity of liver regeneration at 24 hours. Consumption of ethanol was associated with a statistically significant reduction of liver regeneration by both criteria for up to 72 hours after a 70% hepatectomy and delayed the peak of regenerative activity by 24 hours. This inhibiting effect was not related to the presence of alcohol in blood nor to hepatic microsomal enzyme induction by ethanol nor to widespread necrosis of hepatocytes. This effect was reversible after one week of abstinence. This impairment of liver cell renewal by ethanol may be of major significance in the severity and outcome of alcohol-related liver injury.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (880K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • GARCEAU AJ, CHALMERS TC. The natural history of cirrhosis. I. Survival with esophageal varices. N Engl J Med. 1963 Feb 28;268:469–473. [PubMed]
  • Brunt PW, Kew MC, Scheuer PJ, Sherlock S. Studies in alcoholic liver disease in Britain. I. Clinical and pathological patterns related to natural history. Gut. 1974 Jan;15(1):52–58. [PMC free article] [PubMed]
  • Galambos JT. Natural history of alcoholic hepatitis. 3. Histological changes. Gastroenterology. 1972 Dec;63(6):1026–1035. [PubMed]
  • Lieber CS. Pathogenesis and early diagnosis of alcoholic liver injury. N Engl J Med. 1978 Apr 20;298(16):888–893. [PubMed]
  • Wands JR, Carter EA, Bucher NL, Isselbacher KJ. Inhibition of hepatic regeneration in rats by acute and chronic ethanol intoxication. Gastroenterology. 1979 Sep;77(3):528–531. [PubMed]
  • Craig J. Effects of ethanol and ethionine on DNA synthesis during experimental liver regeneration. J Stud Alcohol. 1975 Jan;36(1):148–157. [PubMed]
  • Frank WO, Rayyes AN, Washington A, Holt PR. Effect of acute ethanol administration upon hepatic regeneration. J Lab Clin Med. 1979 Mar;93(3):402–413. [PubMed]
  • DeCarli LM, Lieber CS. Fatty liver in the rat after prolonged intake of ethanol with a nutritionally adequate new liquid diet. J Nutr. 1967 Mar;91(3):331–336. [PubMed]
  • Schneider WC, Greco AE. Incorporation of pyrimidine deoxyribonucleosides into liver lipids and other components. Biochim Biophys Acta. 1971 Feb 11;228(3):610–626. [PubMed]
  • BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. [PubMed]
  • MACDONALD RA, MALLORY GK. Autoradiography using tritiated thymidine. Detection of new cell formation in rat tissues. Lab Invest. 1959 Nov-Dec;8:1547–1562. [PubMed]
  • Joly JG, Doyon C, Peasant Y. Cytochrome P-450 measurement in rat liver homogenate and microsomes. Its use for correction of microsomal losses incurred by differential centrifugation. Drug Metab Dispos. 1975 Nov-Dec;3(6):577–586. [PubMed]
  • Tobon F, Mezey E. Effect of ethanol administration on hepatic ethanol and drug-metabolizing enzymes and on rates of ethanol degradation. J Lab Clin Med. 1971 Jan;77(1):110–121. [PubMed]
  • Feinman L, Baraona E, Matsuzaki S, Korsten M, Lieber CS. Concentration dependence of ethanol metabolism in vivo in rats and man. Alcohol Clin Exp Res. 1978 Oct;2(4):381–385. [PubMed]
  • Rubin E, Hutterer F, Lieber CS. Ethanol increases hepatic smooth endoplasmic reticulum and drug-metabolizing enzymes. Science. 1968 Mar 29;159(3822):1469–1470. [PubMed]
  • Rubin E, Bacchin P, Gang H, Lieber CS. Induction and inhibition of hepatic microsomal and mitochondrial enzymes by ethanol. Lab Invest. 1970 Jun;22(6):569–580. [PubMed]
  • Ishii H, Jean-Gil, Lieber J, Lieber CS. Effect of ethanol on the amount and enzyme activities of hepatic rough and smooth microsomal membranes. Biochim Biophys Acta. 1973 Jan 26;291(2):411–420. [PubMed]
  • Lieber CS, DeCarli LM. Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding. Science. 1968 Nov 22;162(3856):917–918. [PubMed]
  • BUCHER NL. REGENERATION OF MAMMALIAN LIVER. Int Rev Cytol. 1963;15:245–300. [PubMed]
  • Rosenkranz E, Charters AC, 3rd, Orloff MJ. Regeneration in rat liver injured by carbon tetrachloride. Surg Forum. 1975;26:411–412. [PubMed]
  • Lieber CS, Rubin E. Alcoholic fatty liver. N Engl J Med. 1969 Mar 27;280(13):705–708. [PubMed]
  • Sherlock S. Causes and effects of acute liver damage. Scand J Gastroenterol Suppl. 1970;6:187–202. [PubMed]
  • Lischner MW, Alexander JF, Galambos JT. Natural history of alcoholic hepatitis. I. The acute disease. Am J Dig Dis. 1971 Jun;16(6):481–494. [PubMed]
  • Baillie M. Alcohol and the liver. Gut. 1971 Mar;12(3):222–229. [PMC free article] [PubMed]
  • Hasumura Y, Teschke R, Lieber CS. Increased carbon tetrachloride hepatotoxicity, and its mechanism, after chronic ethanol consumption. Gastroenterology. 1974 Mar;66(3):415–422. [PubMed]

Articles from Gut are provided here courtesy of BMJ Publishing Group