Abstract
A critical factor in the extreme shortage of livers for transplantation is frequent failure due to primary non-function of ethanol-induced fatty livers when employed as donor organs (Starzl et all., 1988). Although fatty livers due to ethanol are frequently available in the donor pool since a major source of liver grafts is brain-dead victims of accidents involving alcohol (Butts & Patetta, 1988), surgeons must sometimes discard these organs because of high lipid content. Thus, an examination of the relationship between alcohol, fatty liver, and graft failure following liver transplantation could lead to a larger donor pool of usable organs. With this as a goal, we examined the connection between Kupffer cells and reperfusion injury in ethanol-induced fatty liver since Kupffer cells, which are activated following cold storage and reperfusion (Thurman, Cowper, Marzi, Currin, & Lemasters, 1988), have been implicated in primary non-function. Kupffer cells, when activated, release toxic mediators including cytokines and eicosanoids (Decker, 1990) which may play a role in reperfusion injury following transplantation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Adachi, Y., Bradford, B.U., Gao, W., Bojes, H.K., & Thurman, R.G. (1994). Inactivation of Kupffer cells prevents early alcohol-induced liver injury. Hepatology, 20, 453–460.
Adachi, Y., Moore, L.E., Bradford, B.U., Gao, W., & Thurman, R.G. (1995). Antibiotics prevent liver injury following chronic exposure of rats to ethanol. Gastroenterology, in press.
Arii, S., Monden, K., Itai, S., Sasaoki, T., Shibagaki, M., & Tobe, T. (1988). The three different phases of reticuloendothelial system phagocytic function in rats with liver injury. J.Surg.Res. 45, 314–319.
Bergmeyer, H.U. (1988). Methods of Enzymatic Analysis. New York: Academic Press.
Bernstein, J., Videla, L., & Israel, Y (1973). Metabolic alterations produced in the liver by chronic ethanol administration. Changes related to energetic parameters of the cell. Biochem.J. 134, 515–521.
Bode, C, Kugler, V., & Bode, J.C. (1987). Endotoxemia in patients with alcoholic and non-alcoholic cirrhosis and in subjects with no evidence of chronic liver disease following acute alcohol excess. J Hepatol 4, 8–14.
Bode, J.C, Bode, C, Heidelbach, R., Durr, H.-K., & Martini, G.A. (1984). Jejunal microflora in patients with chronic alcohol abuse. Hepato-gastroenterol, 31, 30–34.
Butts, J.D. & Patetta, M. (1988). North Carolina Medical Examiner System Annual Report 1988. Chapel Hill, N.C. Office of the Chief Medical Examiner and the Staff of the Division of Statistics and Information Services.
Connor, H.D., Gao, W., Nukina, S., Lemasters, J.J., Mason, R.P., & Thurman, R.G. (1992). Free radicals are involved in graft failure following orthotopic liver transplantation: An EPR spin trapping study. Transplantation, 54, 199–204.
Decker, K. (1990). Biologically active products of stimulated liver macrophages (Kupffer cells). Eur J Biochem, 192, 245–261.
Decker, T., Lohmann-Matthes, M.L., Karck, U., Peters, T., & Decker, K. (1989). Comparative study of cytotoxicity, tumor necrosis factor, and prostaglandin release after stimulation of rat Kupffer cells, murine Kupffer cells, and murine inflammatory liver macrophages. J.Leukocyte Biol. 45, 139–146.
D’souza, N.B., Bagby, G.J., Lang, C.H., Deaciuc, I.V., & Spitzer, J.J. (1993). Ethanol alters the metabolic response of isolated, perfused rat liver to a phagocytic stimulus. Alcoholism: Clinical and Experimental Research, 17, 147–154.
Fukui, H., Brauner, B., Bode, J.C., & Bode, C. (1991). Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: Reevaluation with an improved chromogenic assay. Hepatology, 12, 162–169.
Gao, W., Connor, H.D., Lemasters, J.J., Mason, R.P., & Thurman, R.G. (1994). Primary non-function of fatty livers produced by alcohol is associated with a new, antioxidant-insensitive free radical species. Transplantation, in press.
Gao, W., Currin, R.T., Lemasters, J.J., Connor, H.D., Mason, R.P., & Thurman, R.G. (1992). Reperfusion rather than storage injury predominates following long-term (48 hrs) cold storage of grafts in UW solution: Studies with Carolina Rinse in transplanted rat liver. Transplant International, 5, S329–S335.
Goto, M., Lemasters, J.J., & Thurman, R.G. (1993). Activation of voltage-dependent calcium channels in Kupffer cells by chronic treatment with alcohol in the rat. J. of Pharmacol, and Exp. Ther, 267, 1264–1268.
Ji, S., Lemasters, J.J., & Thurman, R.G. (1982). Intralobular hepatic pyridine nucleotide fluorescence: Evaluation of the hypothesis that chronic treatment with ethanol produces pericentral hypoxia. Proc Natl Acad Sci, 80, 5415–5419.
Keller, G.A., West, M.A., Cerra, F.B., & Simmons, R.L. (1985). Multiple system organ failure modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells. Ann.Surg. 201, 87.
Knecht, K.T., Adachi, Y., & Thurman, R.G. (1993). Detection of free radical adducts in the bile of rats treated chronically with intragastric alcohol. Hepatology, 18, 270A. (Abstract)
Lopes, J. & Inniss, W.E. (1969). Electron microscopy of effect of polymyxin B on E. coli lipopolysaccharide. J Bacteriol, 100, 1128–1130.
Martinez, F., Abril, E.R., Earnest, D.L., & Watson, R.R. (1992). Ethanol and cytokine secretion. Alcohol, 9, 455–458.
Marzi, I., Zhong, Z., Zimmermann, F.A., Lemasters, J.J., & Thurman, R.G. (1989). Xanthine and hypoxanthine accumulation during storage may contribute to reperfusion injury following liver transplantation in the rat. Transplantation Proceedings, 21, 1319–1320.(Abstract)
Monden, K., Arii, S., Itai, S., Sasaoki, T., Adachi, Y., Funaki, N., Higashitsuji, H., & Tobe, T. (1991). Enhancement and hepatocyte-modulating effect of chemical mediators and monokines produced by hepatic macrophages in rats with induced sepsis. Research in Experimental Medicine, 191, 177–187.
Monden, K., Arii, S., Itai, S., Sasaoki, T., Adachi, Y, Funaki, N., & Tobe, T. (1991). Enhancement of hepatic macrophages in septic rats and their inhibitory effect on hepatocyte function. J Surg Res, 50, 72–76.
Nanji, A.A., Khettry, U., Sadrzadeh, S.M.H., & Yamanaka, T. (1993). Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am.J.Pathol. 142, 367–373.
Nanji, A.A., Mendenhall, C.L., & French, S.W. (1989). Beef fat prevents alcoholic liver disease in the rat. Alcohol.Clin.Exp.Res. 13, 15–19.
Remmer, H. (1981). Die Wirkungen des Alkohols. Alkoholwirkungen, 17, 1–11.
Satoh, H., Guth, P.H., & Grossman, M.I. (1983). Role of bacteria in gastric ulceration produced by indomethacin in the rat: Cytoprotective action of antibiotics. Gastroenterology, 84, 483–489.
Savier, E., Shedlofsky, S.I., Swim, A.T., Lemasters, J.J., & Thurman, R.G. (1992). The calcium channel blocker nisoldipine minimizes the release of tumor necrosis factor and interleukin-6 following rat liver transplantation. Transplant International, 5, S398–S402.
Stahnke, L.L., Hill, D.B., & Allen, J.I. (1991). TNFa and IL-6 in alcoholic liver disease. In E. Wisse, D.L. Knook, & R.S. McCuskey (Eds.), Cells of the hepatic sinusoid (pp. 472–475). Leiden, The Netherlands: Kupffer cell foundation.
Starzl, T.E., van Thiel, D., Tzakis, A.G., Iwatsuki, S., Todo, S., Marsh, J.W., Koneru, B., Staschak, S., Stieber, A., & Gordon, R.D. (1988). Orthotopic liver transplantation for alcoholic cirrhosis. JAMA, 260, 2542–2544.
Takei, Y, Marzi, I., Kauffman, F.C., Currin, R.T., Lemasters, J.J., & Thurman, R.G. (1990). Increase in survival time of liver transplants by protease inhibitors and a calcium channel blocker, nisoldipine. Transplantation, 50, 14–20.
Thiele, D.L. (1989). Tumor necrosis factor, the acute phase response and the pathogenesis of alcoholic liver disease. Hepatology, 9, 497–499.
Thompson, J.A. & Reitz, R.C. (1978). Effects of ethanol ingestion and dietary fat levels on mitochondrial lipids in male and female rats. Lipids, 13, 540–550.
Thurman, R.G., Cowper, K.B., Marzi, I., Currin, R.T., & Lemasters, J.J. (1988). Activation of Kupffer cells by storage of the liver in Euro-Collins solution. Hepatology, 8, 261. (Abstract)
Thurman, R.G., Marzi, I., Seitz, G., Thies, J., Lemasters, J.J., & Zimmermann, F.A. (1988). Hepatic reperfusion injury following orthotopic liver transplantation in the rat. Transplantation, 46, 502–506.
Tsukamoto, H., Reiderberger, R.D., French, S.W., & Largman, C. (1984).Long-term cannulation model for blood sampling and intragastric infusion in the rat. Am.J.Physiol. 247, R595–R599.
Videla, L., Bernstein, J., & Israel, Y. (1973). Metabolic alteration produced in the liver by chronic alcohol administration. Increased oxidative capacity. Biochem.J. 134, 507–514.
Yamada, S., Mochida, S., Ohno, A., Hirata, K., Ogata. I., Ohta, Y, & Fujiwara, K. (1991). Evidence for enhanced secretory function of hepatic macrophages after long-term ethanol feeding in rats. Liver, 11, 220–224.
Yuki, T. & Thurman, R.G. (1980). The swift increase in alcohol metabolism. Time course for the increase in hepatic oxygen uptake and the involvement of glycolysis. Biochem.J. 186, 119–126.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer Science+Business Media New York
About this chapter
Cite this chapter
Thurman, R.G. et al. (1996). Role of Free Radicals in Failure of Fatty Livers following Liver Transplantation and Alcoholic Liver Injury. In: Snyder, R., et al. Biological Reactive Intermediates V. Advances in Experimental Medicine and Biology, vol 387. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9480-9_31
Download citation
DOI: https://doi.org/10.1007/978-1-4757-9480-9_31
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4757-9482-3
Online ISBN: 978-1-4757-9480-9
eBook Packages: Springer Book Archive