槲皮素对异烟肼诱导肝细胞毒性的保护作用及其机制

doi:10.3969/j.issn.1004-616x.2021.01.003

Abstract

Abstract: OBJECTIVE: To investigate the role of ROS-mediated mitochondrial oxidative damage in isoniazid (INH)-induced hepatotoxicity in vitro and the protective effects from quercetin. METHODS: L-02 hepatocytes in cultures were randomly divided into five groups:isoniazid (10 mmol/L INH), INH + quercetin treatment (10 mmol/L INH and 50 μmol/L quercetin), glutathione (GSH) pretreated (20 mg/mL GSH, 10 mmol/L INH and 50 μmol/L quercetin), glutathione (20 mg/mL GSH) and negative control (equal volume of serum-free medium). After 24 hours of treatment, cell mitochondria were prepared by differential centrifugation, and fluorescent probes DCFH-DA and Rho-123 were used to detect mitochondrial ROS level and membrane potential, Contents of malondialdehyde (MDA) were determined using TBA colorimetry. Contents of protein carbonyl were determined using DPNH colorimetry. Contents of 8-hydroxydeoxyguanine nucleoside (8-OHdG) were determined using ELISA. RESULTS: Compared with the control group, INH-treated cells showed the followings:levels of ROS in mitochondria were elevated (P < 0.01), and membrane potentials were declined (P < 0.01). Compared with the INH group, the quercetin-treated cells showed the followings:mitochondrial ROS levels were reduced (P < 0.01) and membrane potentials were elevated (P < 0.05). Compared with the quercetin-treated group, the glutathione-pretreated cells showed the followings:levels of ROS were lower and the mitochondrial membrane potentials were higher (P < 0.05). Compared with the control group, contents of MDA, protein carbonyl and 8-OHdG were increased after the INH treatment (P < 0.01). Compared with isoniazid group, contents of MDA, protein carbonyl and 8-OHdG in quercetin treatment group were decreased (P < 0.01).Contents of MDA, protein carbonyl and 8-OHdG in the GSH pretreatment group were lower than those in quercetin treatment group (P < 0.05). CONCLUSION: Under the experimental conditions, INH induced oxidative damage of mitochondria in L-02 cells. Quercetin was shown to provide protective effect on INH-induced mitochondrial oxidative damage and the mechanism was related to its inhibition of ROS activities.

Key words: isoniazid, quercetin, mitochondria, reactive oxygen species, oxidative damage

CLC Number:

R965

CHEN Tingyu, CHEN Dayin, SHEN Hong, FU Xuyan, LU Chunfeng. Protective effects of quercetin on isoniazid-induced hepatotoxicity in vitro[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(1): 12-16.

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Protective effects of quercetin on isoniazid-induced hepatotoxicity in vitro

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