Yan-qiong Zhang , Chun-xia Shi , Dan-mei Zhang, Lu-yi Zhang, Lu-wen Wang, Zuo-jiong Gong
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NRF2 agonist SFN and histone deacetylase 6<span> (HDAC6) inhibitor ACY1215<span><span> were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, </span>lactate dehydrogenase (LDH), Fe</span></span></span><sup>2+</sup><span><span>, glutathione (GSH) and </span>malondialdehyde<span><span> (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4<span> (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by </span></span>Western blotting<span> and immunofluorescence.</span></span></span></p></div><div><h3>Results</h3><p>Our results show that NRF2 was activated by SFN. LDH, Fe<sup>2+</sup>, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN <em>in vitro</em> and <em>in vivo</em><span>, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.</span></p></div><div><h3>Conclusion</h3><p>SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.</p><p>Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. <em>J Integr Med</em>. 2023; 21(5): 464–473.</p></div>","PeriodicalId":48599,"journal":{"name":"Journal of Integrative Medicine-Jim","volume":"21 5","pages":"Pages 464-473"},"PeriodicalIF":4.2000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity\",\"authors\":\"Yan-qiong Zhang , Chun-xia Shi , Dan-mei Zhang, Lu-yi Zhang, Lu-wen Wang, Zuo-jiong Gong\",\"doi\":\"10.1016/j.joim.2023.08.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p><span><span>Acute liver failure (ALF) is characterized by </span>severe liver dysfunction<span>, rapid progression and high mortality and is difficult to treat. Studies have found that sulforaphane (SFN), a nuclear factor E2-related </span></span>factor 2<span> (NRF2) agonist, has anti-inflammatory, antioxidant and anticancer effects, and has certain protective effects on neurodegenerative diseases<span>, cancer and liver fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.</span></span></p></div><div><h3>Methods</h3><p><span>Lipopolysaccharide and D-galactosamine were used to induce liver injury </span><em>in vitro</em> and <em>in vivo</em><span>. NRF2 agonist SFN and histone deacetylase 6<span> (HDAC6) inhibitor ACY1215<span><span> were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, </span>lactate dehydrogenase (LDH), Fe</span></span></span><sup>2+</sup><span><span>, glutathione (GSH) and </span>malondialdehyde<span><span> (MDA) were detected. The expression of HDAC6, NRF2, glutathione peroxidase 4<span> (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4) and solute carrier family 7 member 11 (SLC7A11) were detected by </span></span>Western blotting<span> and immunofluorescence.</span></span></span></p></div><div><h3>Results</h3><p>Our results show that NRF2 was activated by SFN. LDH, Fe<sup>2+</sup>, MDA and ACSL4 were downregulated, while GSH, GPX4 and SLC7A11 were upregulated by SFN <em>in vitro</em> and <em>in vivo</em><span>, indicating the inhibitory effect of SFN on ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.</span></p></div><div><h3>Conclusion</h3><p>SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.</p><p>Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. 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Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity
Objective
Acute liver failure (ALF) is characterized by severe liver dysfunction, rapid progression and high mortality and is difficult to treat. Studies 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 fibrosis. This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.
Methods
Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo. NRF2 agonist SFN and histone deacetylase 6 (HDAC6) inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF, respectively. Cell viability, lactate dehydrogenase (LDH), Fe2+, glutathione (GSH) and malondialdehyde (MDA) were detected. The 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 immunofluorescence.
Results
Our results show that NRF2 was activated by SFN. LDH, 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 ferroptosis. Additionally, HDAC6 expression was decreased in the SFN group, indicating that SFN could downregulate the expression of HDAC6 in ALF. After using the HDAC6 inhibitor, ACY1215, SFN further reduced HDAC6 expression and inhibited ferroptosis, indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.
Conclusion
SFN has a protective effect on ALF, and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.
Please cite this article as: Zhang YQ, Shi CX, Zhang DM, Zhang LY, Wang LW, Gong ZJ. Sulforaphane, an NRF2 agonist, alleviates ferroptosis in acute liver failure by regulating HDAC6 activity. J Integr Med. 2023; 21(5): 464–473.
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The predecessor of JIM is the Journal of Chinese Integrative Medicine (Zhong Xi Yi Jie He Xue Bao). With this new, English-language publication, we are committed to make JIM an international platform for publishing high-quality papers on complementary and alternative medicine (CAM) and an open forum in which the different professions and international scholarly communities can exchange views, share research and their clinical experience, discuss CAM education, and confer about issues and problems in our various disciplines and in CAM as a whole in order to promote integrative medicine.
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