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Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease


Richard Kirsch, Mount Sinai Hospital, 600 University Avenue, Toronto, Canada M5G 1X5.
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Abstract: Background/Aims: This study sought to determine whether excess hepatic iron potentiates liver injury in the methionine choline-deficient (MCD) model of non-alcoholic fatty liver disease (NAFLD).

Methods: Iron-loaded rats were fed either MCD or control diets [MCD diet plus choline bitartrate (2 g/kg) and dl-methionine (3 g/kg)] for 4 and 12 weeks, after which liver pathology, hepatic iron, triglyceride, lipid peroxidation products and hydroxyproline (HYP) levels and serum alanine aminotransferase (ALT) levels were evaluated.

Results: Iron supplementation in MCD animals resulted in histologic evidence of hepatic iron overload at 4 and 12 weeks and a 14-fold increase in hepatic iron concentration at 12 weeks (P<0.001). Iron supplementation in these animals was associated with increased lobular necroinflammation at 4 weeks (P<0.02) and decreased hepatic steatosis (P<0.01), hepatic triglyceride levels (P<0.01), hepatic-conjugated dienes (CD; P<0.02) and serum ALT levels (P<0.002) at 12 weeks. Reduced hepatic steatosis (P<0.005) and CD (P<0.01) were apparent by 4 weeks. Iron supplementation was associated with a trend towards increased perivenular fibrosis not hepatic HYP content.

Conclusion: Hepatic iron overload in the MCD model of NAFLD is associated with decreased hepatic lipid, decreased early lipid peroxidation products, increased necroinflammation and a trend towards increased perivenular fibrosis.