Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death

Congcong Zhang; Jiacheng Lin; Chao Zhen; Fang Wang; Xuehua Sun; Xiaoni Kong; Yueqiu Gao

doi:10.1016/j.bbrc.2022.03.011

Amygdalin protects against acetaminophen-induced acute liver failure by reducing inflammatory response and inhibiting hepatocyte death

Biochem Biophys Res Commun. 2022 Apr 30:602:105-112. doi: 10.1016/j.bbrc.2022.03.011. Epub 2022 Mar 3.

Authors

Congcong Zhang¹, Jiacheng Lin², Chao Zhen³, Fang Wang², Xuehua Sun³, Xiaoni Kong⁴, Yueqiu Gao⁵

Affiliations

¹ Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China; Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
² Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
³ Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China.
⁴ Central Laboratory, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China. Electronic address: xiaonikong@shutcm.edu.cn.
⁵ Department of Liver Diseases, ShuGuang Hospital Affiliated to Shanghai University of Chinese Traditional Medicine, Shanghai, China. Electronic address: gaoyueqiu@hotmail.com.

PMID: 35259588
DOI: 10.1016/j.bbrc.2022.03.011

Abstract

Amygdalin is a natural compound from Bitter Apricot Seed which is reported to have anti-inflammatory activity. Acetaminophen (APAP) resulted in drug-induced liver injury is the main cause of acute liver failure (ALI) worldwide and only N-acetylcysteine is the accepted detoxification drug. However, there is no effective medicine to perfect the hepatocyte death and secondary inflammation injury. In this study, we aim to investigate the protective effect of Amygdalin in the APAP-induced acute liver failure mice model. We establish the ALI model via intraperitoneal APAP injection and mice were treated with Amygdalin with intraperitoneal injection. We detected liver enzyme and histological change to evaluate the liver injury. We measured oxidative damage markers and inflammatory cell infiltration of liver tissues. At last, we investigated the mechanism of Amygdalin on protecting hepatocytes. Results showed that Amygdalin reduced ALT/AST level and decreased necrotic area of liver tissue. In addition, Amygdalin reduced the count of MPO+(neutrophils) and F4/80+(macrophages) of the liver and inhibited IL-6, TNF-a, and IL-1b expression. Amygdalin reduced liver SOD and MDA levels and increased Nrf2/NQO1/HO1 protein expression. Moreover, Amygdalin reduced TUNEL+ and P-MLKL + staining cells in liver tissue. Mechanically, Amygdalin promoted phosphorylation of AKT and suppressed JNK/RIP3/MLKL signaling.

Keywords: Acetaminophen; Acute liver failure; Amygdalin; MLKL; Nrf2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetaminophen / adverse effects
Amygdalin* / metabolism
Amygdalin* / pharmacology
Amygdalin* / therapeutic use
Animals
Chemical and Drug Induced Liver Injury* / drug therapy
Chemical and Drug Induced Liver Injury* / metabolism
Chemical and Drug Induced Liver Injury* / prevention & control
Hepatocytes / metabolism
Liver / metabolism
Liver Failure, Acute* / chemically induced
Liver Failure, Acute* / drug therapy
Liver Failure, Acute* / prevention & control
Mice
Oxidative Stress

Substances

Amygdalin
Acetaminophen