Liver injury

Accumulation of lipids in the liver (steatosis) is one possible mechanism for liver toxicity. Several compounds causing necrosis of hepatocytes also cause steatosis. There are, however, some doubts that steatosis would be the primary cause of liver injury. Several compounds cause steatosis (e.g., puro-mycin, cycloheximide) without causing liver injury. Most of the accumulated lipids are triglycerides. In steatosis, the balance between the synthesis and excretion of these lipids has been disturbed (see Table 5.13). 

PlaaGL. 1988. Experimental evaluation of haloalkanes and liver injury. FundamAppl Toxicol 10 563-570. 

Esterbauer, LI. (1985). Lipid peroxidation products formation, chemical properties and biological activation. In Free Radicals in Liver Injury (eds. G. Poli, K. Cheeseman, M.U. Dianzani and T. Slater) pp. 29-47, IRL Press, Oxford. 

The liver was the first organ in the gastrointestinal tract in which the role of ROMs in liver injury was established. Mitchell et al. (1973a, 1973b) demonstrated the roles of several drug-metabolizing enzymes in the formation of... 

There are no studies in humans directly demonstrating increased production of ROM in alcoholic liver disease. However, indirect evidence does support the hypothesis that ROM are involved in the pathogenesis of ethanolic liver injury (Arthur, 1988 Tsukamoto et al., 1990 Nordmann et /., 1992). Basal whole blood... 

The production of free radicals has been implicated in the mechanism of liver injury due to a number of drugs and toxins. These include adtiamycin (Pritsos et al., 1992), halothane (Neuberger and Williams, 1984), phenobar-bital and thiopental (Kanazawa and Ashida, 1991), carbon tetrachloride (Williams and Burk, 1990), 1,1,2,2-tetrachloroethane (Paolini aal., 1992), and paraquat and related bipyridylium compounds (Togashi a al., 1990 De Gray etal., 1991 Kanazawa and Ashida, 1991 Petty etal., 1992). 

Arthur, M.J.P. (1988). Reactive oxygen intermediates and liver injury. J. Hepatol. 6, 125-131. 

Farber, J.L. (1987). Xenobiotics, drug metabolism, and liver injury. Monogr. Pathol. 28, 43-53. 

D. (1991). The decrease of superoxide dismutase activity and depletion of sulfhydryl compounds in ethanol-induced liver injury. Drug Alcohol Depend. 28, 291-294. 

Israel, Y. and Orrego, H. (1981). Hepatocyte demand and substrate supply as factors in susceptibility to alcoholic liver injury pathogenesis and prevention. J. Clin. Gastroenterol. 10, 355-373. 

Jennische, E. (1984). Possible influence of glutathione on postischaemic liver injury. Acta Pathol. Microbiol. Scand. 92, 55-64. 

Kurokawa, T., Nonami, T., Kobayishi, H., Sugiyama, S., Ozawa, T. and Takagj, H. (1992). Effects of long-acting superoxide dismutase on postischaemic liver injury in rats with cirrhosis. J. Hepatol. 14, 268-269. 

Shaw, D.S. and Jayatilleke, E. (1992). The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol-induced liver injury. Life Sci. 50, 2045-2052. 

Halogenated hydrocarbon liver injury FFA-induced pancreatitisf Air pollutants (ozone, SO2, NOa)... 

Iron Overload and Liver Injury 238 3.10 Ischaemic Hepatitis 243... 

Free Badimls in Experimental and Clinical Liver Injury... 

Alcohol abuse is a major clinical problem in many countries and has been the subject of investigation for many years by those interested in determining the molecular basis of ethanol-induced liver dam e (see Lieber, 1990). These intensive and extended efforts have revealed much about the metabolism of ethanol in the liver and about the toxicity of its primary oxidative product, acetaldehyde. They have not, however, folly elucidated the molecular mechanisms that lead to the typical features of alcoholic liver injury steatosis, necrosis and eventually cirrhosis. 

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