A novel synthetic compound, deferiprone-resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice.

Abstract

A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.