Impaired Tissue Content of Iron and Zinc in Mice with Growing Hepatoma 22A and Its Correction with Zinc Sulfate Supplementation

Abstract

The growth of many tumors is known to induce iron and zinc deficiency in the body. Here, we studied the tissue content of iron and zinc, as well as the specific activity of two antioxidant metalloenzymes, catalase (CAT) and superoxide dismutase (SOD), in three distant organs (thymus, liver and spleen) of mice bearing transplantable hepatoma 22a. The revealed alterations in the metal content were compared to changes in organ weights. On day 21 of tumor growth, the non-heme iron content was decreased in all three organs, while that of zinc in the thymus only, as compared to controls. CAT and SOD specific activities were increased in the thymus, while SOD activity was decreased in the liver. At the same time point, thymic involution and splenomegaly were observed to develop. In an attempt to normalize metal content, hepatoma 22a-bearing mice were supplemented with zinc sulfate (22 µg/mL in drinking water) for 3 weeks. Zinc sulfate supplementation partly compensated for zinc deficiency in the thymus, increased zinc content in the liver, and restored iron content in all three organs. It also normalized SOD activity in the liver, while having no effect on both enzymes in other organs. Zinc supplementation did not influence splenic and hepatic weights, but prevented the development of thymic involution. At the same time, the deficiency of both metals in the thymus was restored, while the activity of antioxidant enzymes remained unchanged. It was concluded that thymic involution during hepatoma 22a growth in mice was due to iron and zinc deficiency in this organ, but not to the activity of antioxidant enzymes, whereas splenomegaly was not associated with either. Thus, zinc sulphate exerts a positive effect on metabolism of two vital trace elements, zinc and iron, in mice bearing hepatoma 22a, preserving the thymus as a central immune organ and, at the same time, improving the antioxidant system of the liver.