Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease
Article first published online: 18 SEP 2006
Volume 26, Issue 10, pages 1258–1267, December 2006
How to Cite
Kirsch, R., Sijtsema, H. P., Tlali, M., Marais, A. D. and Hall, P. d. l. M. (2006), Effects of iron overload in a rat nutritional model of non-alcoholic fatty liver disease. Liver International, 26: 1258–1267. doi: 10.1111/j.1478-3231.2006.01329.x
- Issue published online: 18 SEP 2006
- Article first published online: 18 SEP 2006
- Received 10 January 2006,accepted 24 May 2006
- lipid peroxidation;
- methionine choline deficient;
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.