Mechanisms of iron hepatotoxicity

Iron is a vital micronutrient that is essential for fundamental cell functions. However, due to its structural chemistry, water-soluble ferrous iron (Fe2+) is able to exchange electrons with water-insoluble ferric iron (Fe3+), limiting its use and forming the basis of its toxicity. The human body has a natural tendency to retain iron, which leaves it vulnerable to overload and toxicity. Despite this, the liver is highly resilient to iron toxicity, and additional host and environmental factors are required for iron damage to fully manifest. Excess hepatic iron is common to a number of diseases, both hereditary (e.g., hemochromatosis (HC)) or acquired (e.g., chronic liver diseases). In the former, accumulation of iron leads to direct liver damage and slow progression to both micronodular cirrhosis and hepatocellular carcinoma (HCC). In the latter, low to moderate grade excess iron is sufficient to cause an underlying liver disease to worsen and accelerate [1].