Protection of Terminalia belerica Roxb. Against Iron Overload Induced Liver Toxicity: An Account of Its Reducing and Iron Chelating Capacity

Abstract

Excess iron deposition in the liver catalyses the production of Reactive Oxygen Species (ROS) which in turn initiate oxidative damage of protein and nucleic acids leading to several human diseases. The fruits of Terminalia Belerica Roxb. (TB) has been most commonly used not only in stimulating gastrointestinal health, but also in treatment of various hepatic disorders. The present study was aimed to evaluate the ameliorating effect of 70% methanol extract of TB (TBME) on iron overload induced liver injury, along with its in vitro iron chelating and DNA protection studies. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. The biochemical markers of hepatic damage, liver iron, protein carbonyl and hydroxyproline content were measured in response to the oral administration of TBME. The reductive release of ferritin iron by TBME was further studied. The extract exhibited significant iron chelation with IC₅₀ of 27.70 ± 2.27 µg mL^-1 and considerable DNA protection with [P]₅₀ of 1.30 ± 0.01 µg mL^-1. Treatment with different doses (50, 100 and 200 kg body weight) of TBME showed dose dependent reduction in liver iron, lipid peroxidation, protein oxidation, liver fibrosis, serum enzymes and ferritin. The antioxidant enzymes levels were enhanced and the reductive release of ferritin iron increased significantly with gradually increasing concentrations of TBME. From the present results, it appears possible to support that TBME represents beneficial effects on iron overload mediated liver toxicity and hence possibly useful as iron chelating drug for iron overload diseases.