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Autophagy inhibition‐enhanced assembly of the NLRP3 inflammasome is associated with cisplatin‐induced acute injury to the liver and kidneys in rats
Author(s) -
Qu Xiaoyu,
Gao Huan,
Tao Lina,
Zhang Yueming,
Zhai Jinghui,
Song Yanqing,
Zhang Sixi
Publication year - 2019
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22228
Subject(s) - inflammasome , pyrin domain , autophagy , western blot , cisplatin , downregulation and upregulation , caspase 1 , chemistry , liver injury , pharmacology , cancer research , microbiology and biotechnology , receptor , apoptosis , medicine , biology , biochemistry , gene , chemotherapy
Abstract The nucleotide‐binding oligomerization domain‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has a key role in the inflammatory response. We found that cisplatin (7.5, 15 mg/kg, IV) could induce acute injury to the liver and kidneys of rats. Western blot and immunohistochemical analyses showed that expression of NLRP3, caspase‐1 and interleukin‐1β was upregulated significantly in a dose‐dependent manner after cisplatin exposure. Autophagy could inhibit NLRP3 expression and assembly of the NLRP3 inflammasome. Expression of light chain 3 II/I and p62 suggested that autophagy was inhibited during injury to the liver and kidneys. These data suggested that cisplatin might activate NLRP3 by inhibiting autophagy in the liver and kidneys of rats.