An Experimental Study Reveals the Protective Effect of Autophagy against Realgar-Induced Liver Injury via Suppressing ROS-Mediated NLRP3 Inflammasome Pathway
Open Access
- 19 May 2022
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 23 (10), 5697
- https://doi.org/10.3390/ijms23105697
Abstract
Realgar, a poisonous traditional Chinese medicine, has been shown to cause liver injury when used for long periods or overdoses. However, the underlying molecular mechanisms and therapeutic targets have not been fully elucidated. The aim of this study is to explore the role of autophagy in sub-chronic realgar exposure-induced liver injury. Here, the liver injury model was established by continuously administrating mice with 1.35 g/kg realgar for 8 weeks. 3-methyladenine (3-MA) and rapamycin (RAPA) were used to regulate autophagy. The results showed that realgar induced abnormal changes in liver function, pathological morphology, expression of inflammatory cytokines, and upregulated NLRP3 inflammasome pathway in mouse livers. RAPA treatment (an inducer of autophagy) significantly improved realgar-induced liver injury and NLRP3 inflammasome activation, while 3-MA (an inhibitor of autophagy) aggravated the realgar-induced liver injury and NLRP3 inflammasome activation. Furthermore, we found that realgar-induced NLRP3 inflammasome activation in mouse livers is mediated by ROS. RAPA eliminates excessive ROS, inhibits NF-κB nuclear translocation and down-regulates the TXNIP/NLRP3 axis, consequently suppressing ROS-mediated NLRP3 inflammasome activation, which may be the underlying mechanism of the protective effect of autophagy on realgar-induced liver injury. In conclusion, the results of this study suggest that autophagy alleviates realgar-induced liver injury by inhibiting ROS-mediated NLRP3 inflammasome activation. Autophagy may represent a therapeutic target in modulating realgar-induced liver injury.Funding Information
- the Scientific Research Project of Liaoning Provincial Department of Education (JC2019038)
This publication has 37 references indexed in Scilit:
- Caspase-1 activation and mature interleukin-1β release are uncoupled events in monocytesWorld Journal of Biological Chemistry, 2013
- Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver functionProceedings of the National Academy of Sciences of the United States of America, 2012
- Autophagy, mitochondria and oxidative stress: cross-talk and redox signallingBiochemical Journal, 2011
- The Role of Atg Proteins in Autophagosome FormationAnnual Review of Cell and Developmental Biology, 2011
- Defective Hypothalamic Autophagy Directs the Central Pathogenesis of Obesity via the IκB Kinase β (IKKβ)/NF-κB PathwayOnline Journal of Public Health Informatics, 2011
- A role for mitochondria in NLRP3 inflammasome activationNature, 2010
- Comparative proteome study of apoptosis induced by As4S4 in retinoid acid resistant human acute promyelocytic leukemia NB4-R1 cellsLeukemia Research, 2010
- Involvement of the AIM2, NLRC4, and NLRP3 Inflammasomes in Caspase-1 Activation by Listeria monocytogenesJournal of Clinical Immunology, 2010
- Chapter 6 Assays to Assess Autophagy Induction and Fusion of Autophagic Vacuoles with a Degradative Compartment, Using Monodansylcadaverine (MDC) and DQ‐BSAMethods in Enzymology, 2009
- Liver is a Target of Arsenic CarcinogenesisToxicological Sciences, 2008