Mn₃O₄ nanozymes prevent acetaminophen-induced acute liver injury by attenuating oxidative stress and countering inflammation

Acetaminophen (APAP) overdose is steadily becoming the chief reason for drug-induced acute liver failure, yet limited treatment is currently clinically available. Considering that the mechanism of APAP-induced hepato-toxicity is inseparable from oxidative stress and inflammation, a biocompatible Mn3O4 nanozyme mimicking superoxide dismutase (SOD) and catalase (CAT) activities and possessing reactive oxygen species (ROS)-scav-enging capacity and antiapoptotic properties, is reported herein as a promising nanodrug to treat APAP-induced liver injury (AILI). Possessing bioactive enzyme-like functions, Mn3O4 nanoparticles (NPs) can not only reduce the oxidative stress on the liver by decreasing ROS accumulation but also downregulate the infiltration of in-flammatory macrophages that secrete proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Notably, the bifunctional Mn3O4 NPs mediate nuclear factor-erythroid 2 p45-related factor 2 signaling pathway activation and nuclear factor kappa B signaling pathway inhibition to effectively prevent the already fragile APAP-overdosed murine hepatocytes from being attacked again, thus mitigating hepatocyte apoptosis and alleviating APAP-induced liver damage. Thus, the Mn3O4 nanozyme (Mn3O4 NPs) evaluated in this study has potential preventive and therapeutic effects on AILI.