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

Menghua Liu; Haitao Wu; Qianhui Li; Hang Liu; Chongqing Chen; Fan Yin; Hua Wang; Zhengbao Zha; Fei Wang

doi:10.1016/j.jcis.2023.10.019

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

J Colloid Interface Sci. 2024 Jan 15;654(Pt A):83-95. doi: 10.1016/j.jcis.2023.10.019. Epub 2023 Oct 6.

Authors

Menghua Liu¹, Haitao Wu², Qianhui Li³, Hang Liu⁴, Chongqing Chen¹, Fan Yin¹, Hua Wang⁵, Zhengbao Zha⁶, Fei Wang⁷

Affiliations

¹ School of Pharmacy, Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Medical University, Hefei 230032, China.
² Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China; School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
³ China Guangdong Provincial Key Laboratory of Digestive Cancer Research and The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China.
⁴ School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
⁵ Department of Oncology, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China. Electronic address: wanghua@ahmu.edu.cn.
⁶ School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China. Electronic address: zbzha@hfut.edu.cn.
⁷ China Guangdong Provincial Key Laboratory of Digestive Cancer Research and The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong 518107, China. Electronic address: wangf323@mail.sysu.edu.cn.

PMID: 37837854
DOI: 10.1016/j.jcis.2023.10.019

Abstract

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 hepatotoxicity 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)-scavenging 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 inflammatory macrophages that secrete proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, 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.

Keywords: APAP-induced liver injury; Antiapoptosis; Inflammation; Mn(3)O(4) nanozymes; Oxidative damage.

MeSH terms

Acetaminophen* / toxicity
Animals
Antioxidants / pharmacology
Inflammation / chemically induced
Inflammation / drug therapy
Liver*
Mice
Mice, Inbred C57BL
Oxidative Stress
Reactive Oxygen Species / metabolism

Substances

Acetaminophen
Reactive Oxygen Species
Antioxidants