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

Area of Science:

• Hepatology
• Toxicology
• Molecular Biology

Background:

• Drug-induced liver injury (DILI) is a significant clinical concern.
• Doxorubicin (DOX) is a potent chemotherapy agent known to cause liver toxicity.
• Mechanisms of DOX-induced liver injury and potential protective strategies require further investigation.

Purpose of the Study:

• To investigate the therapeutic efficacy of hydrogen in a model of DOX-induced liver injury.
• To elucidate the underlying mechanisms of hydrogen's protective effects against DOX hepatotoxicity.
• To assess the role of the Nrf2/HO-1 pathway in hydrogen's hepatoprotective action.

Main Methods:

• Establishment of a doxorubicin-induced liver injury mouse model.
• Assessment of hepatic function, pathological alterations, oxidative stress, and inflammatory markers.
• Evaluation of apoptosis and the Nrf2/HO-1 signaling pathway.
• In vitro validation using HepG2 cells and an Nrf2 inhibitor.

Main Results:

• Hydrogen treatment significantly reduced DOX-induced liver damage and hepatocyte fibrosis.
• Hydrogen suppressed apoptosis, decreased oxidative stress, and ameliorated liver inflammation.
• The protective effects were linked to the activation of the Nrf2/HO-1 pathway.
• Inhibition of Nrf2 abolished the hepatoprotective effects of hydrogen in HepG2 cells.

Conclusions:

• Hydrogen exhibits significant hepatoprotective effects against doxorubicin-induced liver injury.
• Hydrogen mitigates DOX hepatotoxicity by activating the Nrf2/HO-1 signaling pathway.
• This activation leads to reduced oxidative stress and inflammation, offering a potential therapeutic strategy.