Inhibition Effect of Hydrogen Water on Cisplatin Induced Hepatocyte Injury via Upregulating NFE2L2/HMOX1 Expression

Subjects: Medicine, Pharmacy >> Clinical Medicine submitted time 2024-08-02 Cooperative journals: 《中国全科医学》

WANG Han CHEN Jianhua SONG Shili HAO Zhen HUO Zhongchao LI Sha LI Weixia

Abstract： Background  Cisplatin induced drug-induced liver injury is a common adverse reaction in tumor chemotherapy，which seriously disturbs the clinical treatment of patients. Hydrogen，as a selective antioxidant，has good adjunctive therapeutic effects in various injury related diseases，but its preventive effect and mechanism in cisplatin induced liver injury are not clear. Objective  To study the protective effect and mechanism of hydrogen water on oxidative stress injury of hepatocytes induced by cisplatin. Methods  From June 2022 to June 2023，human normal liver cell line WRL68 were divided into control group，cisplatin group，hydrogen water group，and hydrogen water plus cisplatin group. Control group was cultured with RPMI-1640 medium containing 10% fetal bovine serum for 48 h. Cisplatin group was cultured with RPMI-1640 medium containing 10% fetal bovine serum for 24 h，then added 3 μg/mL cisplatin and continued culturing for 24 h. Hydrogen water group was cultured with 0.6 mg/L hydrogen water medium for 48 h. Hydrogen water+cisplatin group was cultured with 0.6 mg/ L hydrogen water medium for 24h，then added 3 μg/mL cisplatin and continued culturing for 24 h. Then collect cells of each gorup，and hepatocyte activity was detected with CCK-8 method. Cell apoptosis was detected by flow cytometry. Mitochondrial membrane potential（MMP）was detected via Rhodamine 123 fluorescence staining method，and intracellular reactive oxygen species（ROS）levels were detected via DCFH-DA fluorescence probe staining method，the proteins and mRNA expression of nuclear factor erythroid 2-related factor 2（NFE2L2） and heme oxygenase-1（HMOX1） were detected by western blot and RT-qPCR. Results  Compared with the control group，the apoptosis rate and ROS level of cisplatin group increased（P<0.05），while the relative levels of MMP，NFE2L2，HMOX1 protein and mRNA decreased（P<0.05）. There was no statistically significant difference in cell apoptosis rate and ROS level between hydrogen water group and control group（P>0.05），while the relative levels of MMP，NFE2L2，and HMOX1 proteins and mRNA increased（P<0.05）. Compared with cisplatin group，hydrogen water plus cisplatin group decreased in cell apoptosis rate and ROS level（P<0.05），while the relative levels of MMP，NFE2L2，HMOX1 proteins and mRNA increased（P<0.05）. Conclusion  Hydrogen water can inhibit the oxidative stress injury in cisplatin induced hepatocytes via activating NFE2L2/HMOX1 signaling pathway，and improving mitochondrial membrane potential，then alleviate drug-induced liver injury.

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