|Table of Contents|

Protective effect and mechanism of ecdysone on cisplatin induced liver injury in mice

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 02
Page:
241-248
Research Field:
Publishing date:

Info

Title:
Protective effect and mechanism of ecdysone on cisplatin induced liver injury in mice
Author(s):
YIN Qian; YUAN Qin; CHEN Xiangyu; CAI Xiaoming
College of Basic Medicine and Forensic Medicine,North Sichuan Medical University,Sichuan Nanchong 637000,China.
Keywords:
ecdysone; cisplatin; oxidative stress; PDK1; Dnmt3b; MEK5
PACS:
R730.2
DOI:
10.3969/j.issn.1672-4992.2023.02.008
Abstract:
Objective:To investigate the protective effect and mechanism of ecdysone on cisplatin induced liver injury in mice.Methods:Kunming mice and AML12 cells were used to construct cisplatin induced liver injury model in vivo and in vitro.Ecdysone was used to intervene cisplatin group.The pathological morphology of liver tissue was observed by HE staining,the production of intracellular reactive oxygen and apoptosis were observed by ELISA and fluorescence staining,and the expressions of biomarkers related to oxidative stress,inflammation and apoptosis were detected by RT-qPCR.The target was determined by transcriptome sequencing,RT-qPCR and Western blot were used to verify the target genes' expressions of mRNA and protein.Results:Compared with the blank group,the hepatocytes in cisplatin group were loosely arranged,some cells were slightly swollen.The contents of ALT and AST in serum,ROS and MDA in cells increased significantly.And the contents of GSH-PX and SOD in cells decreased significantly,suggesting that cisplatin caused obvious damage to liver function.Compared with cisplatin group,the degree of hepatocyte injury in ecdysone group was significantly reduced,and the above indexes were improved in varying degrees,indicating that ecdysone had a protective effect on liver function.The results of RT-qPCR showed that,in ecdysone group,the mRNA expressions of NF-κB,TNF-α,IL-1β,Caspase-3,Caspase-9,Hmox1,PI3K,Nqo1 decreased significantly and Nrf2 increased(P＜0.01).Transcriptome sequencing and validation experiments showed that ecdysone protects liver function by regulating the low expressions of PDK1 and the high expressions of Dnmt3b and MEK5.Conclusion:Ecdysone has a protective effect on cisplatin induced liver injury through the synergistic regulation of inflammation,oxidative stress and apoptosis.And directly affect the expressions of Dnmt3b,MEK5 and PDK1,which may have a protective effect on liver injury caused by cisplatin.

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Last Update: 1900-01-01