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

J Hepatol. 2007 Dec;47(6):851-9. doi: 10.1016/j.jhep.2007.06.018. Epub 2007 Aug 13.

Abstract

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.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Choline Deficiency / complications*
  • Choline Deficiency / etiology
  • Diet
  • Fatty Liver / etiology*
  • Iron, Dietary / adverse effects*
  • Iron-Dextran Complex / administration & dosage
  • Iron-Dextran Complex / adverse effects
  • Liver Cirrhosis / chemically induced
  • Nutrition Disorders
  • Rats
  • Rats, Wistar

Substances

  • Iron, Dietary
  • Iron-Dextran Complex