Morphologicall investigation of alcohol-induced hepatocyte apoptosis and liver injury in rats

ABSTRACT The aim of this study was to morphologicall investigation of alcohol-induced hepato¬cyte apoptosis and liver injury in rats. A total of 20 male Sprague-Dawley rats were divided into two groups: control, and alcohol treated; each group contain 10 animals. The rats in alcohol treated group was given a daily dose of 6 g/kg ethanol by using intra-gastric intubation. Control group was given the same volume of saline. This application was continued daily for a total of 6 weeks. The end of the experiment all animals were anesthetized. The anesthetized rats were sacrificed and liver tissues were removed for histopathological investigation. Liver damage was examined by using hematoxylin-eosin and apoptosis was determined by terminal-deoxynucleotidyl-transferase mediated dUTP nick end labeling (TUNEL). There existed hepatocyte diffuse steatosis and hemorrhage in alcohol treated group. Our data indicate an enhancement in the activity of TUNEL in hepatocyte apoptosis of the alcholol treated group. The effects of alcohol on liver can be clearly detected as a hepatocyte cell death and liver injury. J. Exp. Clin. Med., 2011; 28:103-106
Keywords:

-,

___

  • Bailey, S.M., Robinson, G., Pinner, A., Chamlee, L., Ulasova, E., Pompilius, M., Page, G.P., Chhieng, D., Jhala, N., Landar, A., Kharbanda, K.K., Ballinger, S., Darley-Usmar, V., 2006. S-adenosylmethionine prevents chronic alcohol-induced mitochondrial dysfunction in the rat liver. Am. J. Physiol. Gastrointest. Liver Physiol. 291, 857-867.
  • Bykov, I., Järveläinen, H., Lindros, K., 2003. L-carnitine alleviates alcohol-induced liver damage in rats: role of tumour necrosis factor-alpha. Alcohol Alcohol. 38, 400-406.
  • Denucci, S.M., Tong, M., Longato, L., Lawton, M., Setshedi, M., Carlson, R.I., Wands, J.R., de la Monte, S.M., 2010. Rat strain differences in susceptibility to alcohol-induced chronic liver injury and hepatic insulin resistance. Gastroenterol. Res. Pract. 312790, Doi: 10.1155/2010/312790
  • Dey, A., Cederbaum, A.I., 2006. Alcohol and oxidative liver injury. Hepatology. 43, 63-74.
  • Farrell, G.C., Larter, C.Z., 2006. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology. 43, 99-112.
  • Feldstein, A.E., Gores, G.J., 2005. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Front. Biosogyci. 10, 3093-3099.
  • Hockenbery, D., 1995. Defining apoptosis. Am. J. Pathol. 146,16–19.
  • Kanter, M., 2010. Protective effect of quercetin on liver damage induced by biliary obstruction in rats. J. Mol. Histol. 41, 395-402.
  • Kerr, W.C., Fillmore, K.M., Marvy, P., 2000. Beverage-specific alcohol consumption and cirrhosis mortality in a group of English-speaking beerdrinking countries. Addiction. 95, 339-346.
  • Lambert, J.C., Zhou, Z., Kang, Y.J., 2003. Suppression of Fas-mediated signaling pathway is involved in zinc inhibition of ethanol-induced liver apoptosis. Exp. Biol. Med. 228, 406-412. Lemasters, J.J., 2005. Dying a thousand deaths: redundant pathways from different organelles to apoptosis and necrosis. Gastroenterol. 129, 351–360.
  • Nanji, A.A., Khettry, U., Sadrzadeh, S. M., 1994. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver disease. Proc. Soc. Exp. Biol. Med. 205, 243-247.
  • Nanji, A.A., Zakim, D., 1996. In: Zakim D., Boyer I. D. (eds.), Alcoholic liver disease. Hepatology: A Textbook of Liver disease, 3rd edn. Saunders, Philadelphia PA, 891-961.
  • Natori, S., Rust, C., Stadheim, L.M., Srinivasan, A., Burgart, L.J., Gores, G.J., 2001. Hepatocyte apoptosis is a pathologic feature of human alcoholic hepatitis. J. Hepatol. 34, 248-253.
  • Omagari, K., Morikawa, S., Nagaoka, S., Sadakane, Y., Sato, M., Hamasaki, M., Kato, S., Masuda, J., Osabe, M., Kadota, T., Sera, K., 2009. Predictive factors for the development or regression of fatty liver in Japanese adults. J. Clin. Biochem. Nutr. 45, 56-67.
  • Pani, G., Fusco, S., Colavitti, R., Borrello, S., Maggiano, N., Cravero, A.A., 2004. Abrogation of hepatocyte apoptosis and early appearance of liver dysplasia in ethanol-fed p53-deficient mice. Biochem. Biophys. Res. Commun. 325, 97-100.
  • Ramalho, R.M., Cortez-Pinto, H., Castro, R.E., Solá, S., Costa, A., Moura, M.C., Camilo, M.E., Rodrigues, C.M., 2006. Apoptosis and Bcl-2 expression in the livers of patients with steatohepatitis. Eur. J. Gastroenterol. Hepatol. 18, 21-29.
  • Ribeiro, P.S., Cortez-Pinto, H., Solá, S., Castro, R.E., Ramalho, R.M., Baptista, A., Moura, M.C., Camilo, M.E., Rodrigues, C.M., 2004. Hepatocyte apoptosis, expression of death receptors, and activation of NF-kappaB in the liver of nonalcoholic and alcoholic steatohepatitis patients. Am. J. Gastroenterol. 99, 1708-1717.
  • Stewart, S., Jones, D., Day, C. P., 2001. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol. Med. 7, 408–413.
  • Thornberry, N.A., Lazebnik, Y., 1998. Caspases: enemies within. Science. 281, 1312-1316.
  • Tsukamoto, H., Takei, Y., McClain, C.J., Joshi-Barve, S., Hill, D., Schmidt, J., Deaciuc, I., Barve, S., Colell, A., Garcia-Ruiz, C., Kaplowitz, N., Fernandez-Checa, J.C., Yokoyama, H., Okamura, Y., Nakamura, Y., Ishii, H., Chawla, R.K., Barve, S., Joshi-Barve, S., Watson, W., Nelson, W., Lin, M., Ohata, M., Motomura, K., Enomoto, N., Ikejima, K., Kitamura, T., Oide, H., Hirose, M., Bradford, B.U., Rivera, C.A., Kono, H., Peter, S., Yamashina, S., Konno, A., Ishikawa, M., Shimizu, H., Sato, N., Thurman, R., 2001. How is the liver primed or sensitized for alcoholic liver disease? Alcohol Clin. Exp. Res. 25, 171-181.
  • Younossi, Z.M., 2008. Review article: current management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Aliment Pharmacol. Ther. 28, 2-12.
  • Zhou, Z., Sun, X., Kang, Y.J., 2001. Ethanol-induced apoptosis in mouse liver: Fas- and cytochrome c-mediated caspase-3 activation pathway. Am. J. Pathol. 159, 329-338.
  • Ziol, M., Tepper, M., Lohez, M., Arcangeli, G., Ganne, N., Christidis, C., Trinchet, J.C., Beaugrand, M., Guillet, J.G., Guettier, C., 2001. Clinical and biological relevance of hepatocyte apoptosis in alcoholic hepatitis. J. Hepatol. 34, 254-260.