A biochemical and histopathological investigation on the effects of metallothioneins against oxidative stress caused by thallium toxicity in rat liver cells

In the present study, effects of metalllothioneins against the oxidative stress as a result of thallium intoxication were investigated on rat liver. Male wistar rats weighing 200-250 g were studied in 6 groups including control, thallium (32 mg/kg) intoxicated, metallothionein (1 and 2.5 mg/kg) administrated-thallium (32 mg/kg) intoxicated and metallothionein (1 and 2.5 mg/kg) administrated animals. Experiments were conducted by using biochemical and histopathological techniques. Thallium concentrations and total protein levels in the liver tissue were determined. Changes in the levels of total glutathione were determined and malonedialdehyde levels as an indicator of lipid peroxidation were measured. Hydrogen peroxide levels, as a marker of reactive oxygen species, were measured to support lipid peroxidation findings and to determine oxidative stress. Activities of antioxidant enzymes, superoxide dismutase and glutathione peroxidase were measured. Superoxide dismutase enzyme levels were also determined immunohistochemically to verify the enzyme activity results. Histopathological examinations were conducted on light and electron microscopic levels.The results showed that metallothionein increases the antioxidant capacity of cells by decreasing the levels of intracellular free thallium, preventing the interactions between thallium and sulfhydril-rich proteins and serving as a scavenger of reactive oxygen species inside the cells. Increased antioxidant capacity results in a decrease in lipid peroxidation and conservation of membranous structures of the cell.Both biochemical and histopathological findings of this study showed that metallothionein at 2.5 mg/kg dose is effective on preventing the cellular and tissue damage caused by oxidative stress in thallium intoxication. In this study in vivo interactions between thallium, metallothionein and antioxidant components of the cell were exhibited for the first time.Keywords: Metallothionein, Thallium, Oxidative stress, Liver, Histopathology