Protective effects of Lactobacillus rhamnosus GG and 5-methoxyindole-3-acetic acid against diquat-induced acute liver injury involve activation of the Nrf2/HO-1 signaling pathway.

BACKGROUND

Diquat (DQ), a widely used bipyridyl herbicide, induces acute liver injury primarily through oxidative stress, and effective targeted therapies remain lacking. Lactobacillus rhamnosus GG (LGG) exhibits antioxidant potential, but its role in DQ-induced liver injury has not been fully clarified. This study investigated the protective effects of LGG and its associated metabolite 5-methoxyindole-3-acetic acid (5-MIAA) and explored the underlying mechanisms.

METHODS

A DQ-induced acute liver injury model was established in C57BL/6 mice with LGG pretreatment and Nrf2 inhibitor (ML385) intervention. Liver function, histopathology, oxidative stress markers, and Nrf2/HO-1 expression were assessed. In vitro, DQ-treated HepG2 cells were exposed to varying concentrations of 5-MIAA, and cell viability and pathway-related molecules were analyzed using CCK-8 and Western blot.

RESULTS

DQ exposure markedly elevated ALT and AST levels, aggravated hepatic necrosis and inflammation, increased ROS and MDA levels, decreased SOD and GSH-Px activities, and suppressed Nrf2 and HO-1 expression. LGG pretreatment significantly alleviated liver injury and oxidative stress while restoring Nrf2/HO-1 expression. ML385 partially attenuated the protective effects of LGG. In vitro, 5-MIAA dose-dependently improved viability of DQ-injured HepG2 cells and upregulated Nrf2 and HO-1 expression.

CONCLUSION

LGG mitigates DQ-induced acute liver injury by activating the Nrf2/HO-1 pathway and reducing oxidative stress, while 5-MIAA may represent a potential bioactive compound with similar hepatoprotective effects. These findings provide mechanistic support for probiotic-based strategies in toxicant-induced liver injury.