Methane Alleviates Acetaminophen-Induced Liver Injury by Inhibiting Inflammation, Oxidative Stress, Endoplasmic Reticulum Stress, and Apoptosis through the Nrf2HO-1NQO1 Signaling Pathway

Abstract EN

Acetaminophen- (APAP-) induced hepatic injury is an important clinical challenge.

Oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress (ERS) contribute to the pathogenesis.

Methane has potential anti-inflammatory, antioxidant, and antiapoptotic properties.

This project was aimed at studying the protective effects and relative mechanisms of methane in APAP-induced liver injury.

In the in vivo experiment, C57BL/6 mice were treated with APAP (400 mg/kg) to induce hepatic injury followed by methane-rich saline (MRS) 10 ml/kg i.p.

after 12 and 24 h.

We observed that MRS alleviated the histopathological lesions in the liver, decreased serum aminotransferase levels, reduced the levels of inflammatory cytokines, suppressed the nuclear factor-κB expression.

Further, we found that MRS relieved oxidative stress by regulating the Nrf2/HO-1/NQO1 signaling pathway and their downstream products after APAP challenge.

MRS also regulated proteins associated with ERS-induced apoptosis.

In the in vitro experiment, the L-02 cell line was treated with APAP (10 mM) to induce hepatic injury.

We found that a methane-rich medium decreased the levels of reactive oxygen species (DHE fluorescent staining), inhibited apoptosis (cell flow test), and regulated the Nrf2/HO-1/NQO1 signaling pathway.

Our data indicated that MRS prevented APAP-induced hepatic injury via anti-inflammatory, antioxidant, anti-ERS, and antiapoptotic properties involving the Nrf2/HO-1/NQO1 signaling pathway.