[Hesperetin Alleviates Doxorubicin-Induced Cytotoxicity in H9c2 Cells by Activating SIRT1/NRF2 Signaling].

Autor:	Li X; Department of Pharmacology and Toxicology, Xi'an Medical University, Xi'an 710021, China., Yan A; Department of Pathology, Xi'an Medical University, Xi'an 710021, China., Chang J; Department of Physiology, Xi'an Medical University, Xi'an 710021, China., Li F; Department of Pharmacology and Toxicology, Xi'an Medical University, Xi'an 710021, China., Zhu J; Department of Physiology, Xi'an Medical University, Xi'an 710021, China.
Jazyk:	čínština
Zdroj:	Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition [Sichuan Da Xue Xue Bao Yi Xue Ban] 2023 Sep; Vol. 54 (5), pp. 947-953.
DOI:	10.12182/20230960207
Abstrakt:	Objective: To investigate whether hesperetin (Hes) alleviates doxorubicin (DOX)-induced cardiomyocytotoxicity by reducing oxidative stress via regulating silent information regulator 1 (SIRT1)/nuclear transcription factor E2-related factor 2 (NRF2) signaling in H9c2 cells. Methods: H9c2 cells were treated with DOX to establish the cardiotoxicity model and were randomly assigned to four groups, a control group (Control) and three treatment groups, receiving respectively DOX (the DOX group), Hes+DOX (the DOX+Hes group), and Hes+SIRT1 inhibitor EX527+DOX (the DOX+Hes+EX527 group). Cellular morphology was observed by the light microscope. Cell viability was evaluated by CCK-8. DOX-induced apoptosis in H9c2 cells was examined by flow cytometry. The levels of reactive oxygen species (ROS) in the H9c2 cells of the four groups were determied with 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. The activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), and SIRT1 as well as the malondialdehyde (MDA) content were measured using ELISA kits. The expressions of cleaved caspase-3, cytochrome c, SIRT1, Ac-FOXO1, NRF2, and heme oxygenase 1 (HO-1) were determined by Western blot. Results: Compared with the Control group, the DOX group showed swollen cellular morphology, decreased cell density and viability, and increased LDH activity in the medium ( P <0.01); both apoptosis and the expression of cleaved caspase-3 and cytochrome c increased ( P <0.01); the activities of CAT and SOD decreased while the contents of MDA and ROS increased ( P <0.01); the expression of SIRT1, NRF2, and HO-1 decreased, the activity of SIRT1 decreased, and the expression of Ac-FOXO1 increased ( P <0.01). Compared with the DOX group, the DOX+Hes group showed improved cellular morphology, increased cell density and viability, and decreased LDH activity in the medium ( P <0.01); the apoptosis and the expression of cleaved caspase-3 and cytochrome c decreased ( P <0.01); the activities of CAT and SOD increased while the levels of MDA and ROS decreased ( P <0.01); the expression of SIRT1, NRF2, and HO-1 increased, the activity of SIRT1 increased, and the expression of Ac-FOXO1 decreased ( P <0.01). Comparison of the findings for the DOX+Hes group and the DOX+Hes+EX527 group showed that EX527 could block the protective effects of Hes against DOX-induced cell injury, oxidative stress, and SIRT1/NRF2 signaling. Conclusion: Hes inhibits oxidative stress and apoptosis via regulating SIRT1/NRF2 signaling, thereby reducing DOX-induced cardiotoxicity in H9c2 cells. (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)
Databáze:	MEDLINE
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