Open AccessMgIG exerts therapeutic effects on crizotinib‐induced hepatotoxicity by limiting ROS ‐mediated autophagy and pyroptosis
Author(s) -
Li Min,
Wang Chenxiang,
Yu Zheng,
Lan Qin,
Xu Shaolin,
Ye Zhongjiang,
Li Rongqi,
Ying Lili,
Zhang Xiuhua,
Zhou Ziye
Publication year - 2022
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.17474
Subject(s) - pyroptosis , reactive oxygen species , autophagy , flow cytometry , mitochondrial ros , chemistry , apoptosis , panax notoginseng , pharmacology , programmed cell death , cancer research , biology , microbiology and biotechnology , biochemistry , medicine , alternative medicine , pathology
Abstract Crizotinib (CRIZO) has been widely employed to treat non‐small‐cell lung cancer. However, hepatic inflammatory injury is the major toxicity of CRIZO, which limits its clinical application, and the underlying mechanism of CRIZO‐induced hepatotoxicity has not been fully explored. Herein, we used cell counting kit‐8 assay and flow cytometry to detect CRIZO‐induced cytotoxicity on human hepatocytes (HL‐7702). CRIZO significantly reduced the survival rate of hepatocytes in a dose‐dependent manner. Furthermore, the reactive oxygen species (ROS) assay kit showed that CRIZO treatment strongly increased the level of ROS. In addition, CRIZO treatment caused the appearance of balloon‐like bubbles and autophagosomes in HL‐7702 cells. Subsequently, Western blotting, quantitative real‐time PCR and ELISA assays revealed that ROS‐mediated pyroptosis and autophagy contributed to CRIZO‐induced hepatic injury. Based on the role of ROS in CRIZO‐induced hepatotoxicity, magnesium isoglycyrrhizinate (MgIG) was used as an intervention drug. MgIG activated the Nrf2/HO‐1 signalling pathway and reduced ROS level. Additionally, MgIG suppressed hepatic inflammation by inhibiting NF‐κB activity, thereby reducing CRIZO‐induced hepatotoxicity. In conclusion, CRIZO promoted autophagy activation and pyroptosis via the accumulation of ROS in HL‐7702 cells. MgIG exerts therapeutic effects on CRIZO‐induced hepatotoxicity by decreasing the level of ROS.