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Sulforaphane,an NRF2 agonist,alleviates ferroptosis in acute liver failure by regulating HDAC6 activity

Journal of Integrative Medicine 2023年第5期21卷 464-473页

作者： Yan-qiong Zhang Chun-xia Shi Dan-mei Zhang Lu-yi Zhang Lu-wen Wang Zuo-jiong Gong Department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhan 430060Hubei ProvinceChina

Objective Acute liver failure(ALF)is characterized by severe liver dysfunction,rapid progression and high mortality and is difficult to *** have found that sulforaphane(SFN),a nuclear factor E2-related factor 2(NRF2)agonist,has anti-inflammatory,antioxidant and anticancer effects,and has certain protective effects on neurodegenerative diseases,cancer and liver *** paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of *** Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in ***2 agonist SFN and histone deacetylase 6(HDAC6)inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF,*** viability,lactate dehydrogenase(LDH),Fe2+,glutathione(GSH)and malondialdehyde(MDA)were *** expression of HDAC6,NRF2,glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blotting and *** Our results show that NRF2 was activated by ***,Fe2+,MDA and ACSL4 were downregulated,while GSH,GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo,indicating the inhibitory effect of SFN on ***,HDAC6 expression was decreased in the SFN group,indicating that SFN could downregulate the expression of HDAC6 in *** using the HDAC6 inhibitor,ACY1215,SFN further reduced HDAC6 expression and inhibited ferroptosis,indicating that SFN may inhibit ferroptosis by regulating HDAC6 *** SFN has a protective effect on ALF,and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.

关键词： acuteliverfailure Sulforaphane NRF2 HDAC6 Ferroptosis

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