# Hydrogen Mitigated Doxorubicin-Induced Liver Injury via Nrf2/HO-1 Pathway Activation

## TL;DR

Hydrogen protects the liver from doxorubicin damage by activating a specific antioxidant pathway.

## Contribution

This study reveals hydrogen's novel protective role against doxorubicin-induced liver injury via the Nrf2/HO-1 pathway.

## Key findings

- Hydrogen treatment reduced liver damage and fibrosis in doxorubicin-treated mice.
- Hydrogen suppressed apoptosis and oxidative stress in liver tissue.
- The protective effect of hydrogen was blocked by an Nrf2 inhibitor in HepG2 cells.

## Abstract

Drug-induced liver injury constitutes a major concern within the spectrum of drug-related pathologies. The precise mechanisms underlying doxorubicin (DOX)-induced liver injury remain inadequately elucidated. Hydrogen is known for its selective antioxidant properties and favorable safety profile; however, its protective effects against DOX-induced liver injury have not been fully clarified. In this study, a model of DOX-induced liver injury was established to evaluate hepatic function and pathological alteration, thereby assessing the therapeutic efficacy of hydrogen. Further investigations were conducted to quantify oxidative stress and inflammatory markers to elucidate the potential mechanisms involved. Hydrogen treatment significantly mitigated DOX-induced liver damage and inhibited hepatocyte fibrosis. Hydrogen was found to suppress apoptosis, reduce oxidative stress levels, and ameliorate inflammatory responses in the liver tissue of DOX mice. The protective effect was predominantly facilitated by the modulation of the Nrf2/HO-1 pathway. Importantly, the hepatoprotective effect of hydrogen was negated following the administration of an Nrf2 inhibitor in HepG2 cells. These results suggest that hydrogen may mitigate DOX-induced liver injury by activating the Nrf2/HO-1 signaling pathway, consequently diminishing oxidative stress and inflammatory responses.