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 peroxidati on (LP) induced by an hepatotoxic compound, such as alcohol. To invest igate 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 ethano l (36% of total calories) or isocaloric carbohydrate with or without d ietary carbonyl iron (0.5% w/v) for 12 weeks. Serum alanine aminotrans ferase (ALT) levels were greatly elevated in rats fed a high-fat diet containing both ethanol and iron (EtOH-Fe). Morphologically, slight fi brosis with fatty infiltration and occasional iron deposits were found in the liver of rats fed EtOH-Fe. Moreover, type 4 collagen was defin itely stained in the liver of the EtOH-Fe-fed group. However, no evide nce of fibrosis was seen in the liver of rats other than the EtOH-Fe-f ed group. Furthermore, there was no evidence of secondary hemochromato sis in the rat fed EtOH-Fe or a high-fat diet containing iron. The hep atic content of hydroxyproline (HP) was significantly increased in EtO H-Fe-fed rats as compared to rats other than the EtOH-Fe-fed group. Si milarly, microsomal malondialdehyde (MDA) levels were relatively eleva ted in EtOH-Fe-fed rats. These results demonstrate the evidence of a s ynergistic effect between alcohol and iron in producing alcoholic live r fibrosis through the enhancement of LP. This new rat model (Fukudai Model) may be useful for further studies in the pathogenesis of ALD.