Metallothioneins (MTs) are cysteine-rich proteins capable of scavenging free radicals and sequestering metal ions. In the liver, these proteins are involved in copper and zinc metabolism, in the chelation of heavy metals, and in protection against oxidative damage. Because of their properties, MTs are involved in many liver diseases, which can be sorted into the following:
1. Metal storage liver diseases. Zinc, which is an important anticopper agent for Wilson's disease, acts by increasing the concentration of MTs in the enterocytes, thereby reducing metal absorption. Copper also accumulates in the liver in cholestatic diseases, in which MTs are reportedly overexpressed and induced by ursodeoxycholic acid (UDCA), the main drug used to treat cholestasis. The role of MTs in hemochromatosis, an iron-accumulating disease, has yet to be established; but in animal models, it has been suggested that zinc, by increasing MT concentration, could exert a beneficial effect.
2. Toxic liver diseases. By sequestering metal ions and scavenging free radicals, MTs protect against damage caused by exogenous toxic substances, such as cadmium and arsenic, and by the toxic effects on hepatocytes of ethanol and at in alcoholic and nonalcoholic liver diseases.
3. Chronic viral hepatitis. By lowering the inflammatory injury, MTs have a protective action against chronic liver damage; a relationship has also been described between MTs and the severity of liver disease and the response to therapy.
4. Hepatocellular carcinoma. MTs are downexpressed and inversely correlated with tumor stage; an inverse correlation has also been reported between MT concentrations and response to platinum chemotherapy.
Given the ability of zinc to strongly induce MT synthesis, zinc supplementation could be useful not only in Wilson's disease, but also in other liver diseases in which MTs exert a protective effect.
