# Therapeutic Potential of Deferiprone–Resveratrol Hybrid (DFP-RVT) Against Hepatic Iron Overload in β-Thalassemia Mice: A Proteomic Analysis

## TL;DR

This study explores how a drug combination helps reduce liver damage from iron overload in a mouse model of β-thalassemia by restoring mitochondrial function.

## Contribution

The study introduces a novel hybrid drug, DFP-RVT, and demonstrates its therapeutic potential in reversing mitochondrial dysfunction caused by iron overload.

## Key findings

- Iron overload significantly downregulated mitochondrial proteins like frataxin in β-thalassemia mice.
- DFP-RVT treatment restored mitochondrial proteins involved in energy metabolism and respiratory chain function.
- Proteomic analysis showed DFP-RVT reversed iron-induced mitochondrial protein dysregulation.

## Abstract

Iron overload is a major pathological feature of β-thalassemia and a key driver of hepatic injury through oxidative stress and mitochondrial dysfunction. This study investigated the molecular effects of iron overload on liver mitochondria and evaluated the therapeutic potential of a deferiprone–resveratrol hybrid (DFP-RVT) in a β-thalassemia mouse model. Proteomic analysis was performed on liver tissues from baseline control, iron-overloaded, and DFP-RVT-treated mice to identify differentially expressed proteins and affected pathways. Iron overload resulted in marked downregulation of mitochondrial proteins, particularly components of oxidative phosphorylation and iron–sulfur cluster-associated pathways, including frataxin. In contrast, DFP-RVT treatment restored the expression of multiple mitochondrial proteins involved in respiratory chain function and energy metabolism. Comparative proteomic profiling revealed opposing regulation patterns between iron-overloaded and DFP-RVT-treated groups, indicating recovery of mitochondrial integrity following iron chelation therapy. These findings suggest that iron-induced hepatic injury in β-thalassemia is closely linked to mitochondrial protein dysregulation and that DFP-RVT may mitigate this process by restoring mitochondrial protein expression and iron homeostasis. This study provides mechanistic insight into iron-mediated mitochondrial dysfunction and supports the therapeutic potential of DFP-RVT for iron overload-associated liver injury.