Iron preloading aggravates nutritional steatohepatitis in rats by increasing apoptotic cell death.

BACKGROUND/AIMS: High serum ferritin and liver iron concentrations were found in some patients with NASH, suggesting a role for iron as a co-factor that aggravates liver injury. The aim of this study is to investigate the effects of parenteral iron in a rat model of NASH induced by a methionine choline deficient diet (MCDD).

METHODS

Wistar rats were divided into 1 - Control, 2 - Iron (Fe), 3 - MCDD, 4 - MCDD&Fe groups. Iron dextran 100mg/kg was administered intra-muscularly in groups 2 and 4. All rats were fed MCDD, Groups 1 and 2 were supplied with choline and methionine. Blood and tissue samples were obtained after 4weeks.

RESULTS

The iron injection alone did not affect the liver whereas MCDD led to steatohepatitis. Iron worsened steatosis without any obvious effect on accompanying inflammation. It aggravated tissue injury by increasing apoptosis. Liver fibrosis was observed only in 3 out of 10 rats in the MCDD&Fe group.

CONCLUSIONS

Observation of liver fibrosis only in the MCDD&Fe group suggests that iron induced increase in apoptosis contributes to the development of fibrosis at an earlier time than expected.