The effects of iron overload or deficiency in thioacetamide induced acute liver injury

Background/aim: Increase in hepatic iron concentration (HIC) may augment the severity and progression while reduction of HIC may attenuate a variety of chronic, non-hemochromatotic liver disorders. It is not known whether manipulations in the HIC may exacerbate or attenuate acute liver injury (ALI) from various toxins, like thioacetamide (TAA). Methods: Rats were randomly divided into 6 subgroups: 2 control with “normal” hepatic iron concentration (HIC), 2 that were subjected to parenterally iron overload (PIIO), 1 that was subjected to orally induced iron overload (OIIO), 1 that received repeated phlebotomies. Four groups (one group from each category) were also subjected to TAA toxicity. Results: TAA administration to control rats induced severe hepatic cell necrosis and apoptosis associated with a tremendous increase in serum aminotransaminases and depletion of hepatic glutathione and anti-oxidative parameters. OIIO and PIIO increased HIC by 370% and 2041% respectively. OIIO and PIIO induced hepatocellular (parenchymal) and reticuloendothelial iron overload respectively. Compared to the control group with “normal” HIC, TAA administration induced an exacerbated ALI in the OIIO rats but an ALI of a similar magnitude, in the PIIO rats. TAA administration to the phlebotomized rats caused an elevation in serum aminotransaminases that was of similar magnitude to the control group, but with less hepatic inflammatory infiltrate, higher hepatic glutathione content and a better hepatic anti-oxidative enzyme profile. Conclusions: Hepatocellular iron overload, but not reticuloendothelial iron overload exacerbates TAA induced ALI. Phlebotomy may improve the hepatic anti-oxidative milieu and thus may mildly attenuate TAA induced ALI.