HEPATIC-FIBROSIS IN RATS FED A LIQUID DIET WITH ETHANOL AND CARBONYL IRON

It is known that iron acts as a co-factor to catalyze lipid peroxidation (LP) induced by an hepatotoxic compound, such as alcohol. To investigate the role of iron in the pathogenesis of alcoholic liver disease (ALD), we developed a new experimental rat model. Male Sprague-Dawley rats were pair-fed ad libitum a liquid high-fat diet containing ethanol (36% of total calories) or isocaloric carbohydrate with or without dietary carbonyl iron (0.5% w/v) for 12 weeks. Serum alanine aminotransferase (ALT) levels were greatly elevated in rats fed a high-fat diet containing both ethanol and iron (EtOH-Fe). Morphologically, slight fibrosis with fatty infiltration and occasional iron deposits were found in the liver of rats fed EtOH-Fe. Moreover, type 4 collagen was definitely stained in the liver of the EtOH-Fe-fed group. However, no evidence of fibrosis was seen in the liver of rats other than the EtOH-Fe-fed group. Furthermore, there was no evidence of secondary hemochromatosis in the rat fed EtOH-Fe or a high-fat diet containing iron. The hepatic content of hydroxyproline (HP) was significantly increased in EtOH-Fe-fed rats as compared to rats other than the EtOH-Fe-fed group. Similarly, microsomal malondialdehyde (MDA) levels were relatively elevated in EtOH-Fe-fed rats. These results demonstrate the evidence of a synergistic effect between alcohol and iron in producing alcoholic liver fibrosis through the enhancement of LP. This new rat model (Fukudai Model) may be useful for further studies in the pathogenesis of ALD.