Iron Overload Decreases the Protective Effect of Tumour Necrosis Factor-α on Rat Hepatocytes Exposed to Oxidative Stress

Abstract

Background: Intracellular iron can participate in the formation of free radicals, leading to liver cell damage. This may be prevented by the ability of ferritin to oxidize and store iron. Tumour necrosis factor alpha (TNF- α ) has been shown to increase the ferritin synthesis. In the liver, cytokines are secreted by activated Kupffer cells and T-lymphocytes. The aim of this study was to investigate the effects of TNF- α on normal and iron-loaded rat hepatocytes exposed to oxidative stress. Methods: Primary cultures of hepatocytes from rats fed a normal rat chow or a carbonyl iron-enriched diet were incubated with TNF- α before incubation with tert -butyl hydroperoxide. Malondialdehyde concentrations, activities of lactate dehydrogenase, ferritin H and manganese superoxide dismutase mRNA and ferritin H protein were analysed. The total amounts of glutathione and chelatable iron were measured. Results: TNF- α diminished the concentrations of malondialdehyde and activities of lactate dehydrogenase in hepatocytes exposed to tert -butyl hydroperoxide. This was seen in hepatocytes from normal but not iron-loaded animals. The transcription of manganese-superoxide dismutase mRNA was increased in both cell types, whereas total glutathione contents of cells were unaffected. The transcription and translation of ferritin H was induced in cells from normal but not from iron-loaded animals. The amount of chelatable iron was significantly lowered only in hepatocytes from normal rats. Conclusions: TNF- α protects rat hepatocytes from normal but not iron-loaded rats from oxidative stress. The protection may be due to an induction of the ferritin synthesis.

• Cytokine Protection
• Hepatocytes
• Iron
• Oxidative Stress