EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro
Excessive consumption of acetaminophen (APAP) has emerged as the primary culprit behind drug-induced liver injury (DILI), with N-acetylcysteine serving as the principal antidote. However, use of N-acetylcysteine is limited to the early stages of APAP-induced DILI and may cause adverse side effects....
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| Format: | Article |
| Language: | English |
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2025-01-01
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| Series: | Acta Materia Medica |
| Online Access: | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0087 |
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| author | Zijun Ouyang Tao Zhang Mengting Liu Fufu Li Hui Guo Yanhui Li Jieyu Chen Feiyang Wang Yang Sun Dong Liu Haiyan Sun |
| author_facet | Zijun Ouyang Tao Zhang Mengting Liu Fufu Li Hui Guo Yanhui Li Jieyu Chen Feiyang Wang Yang Sun Dong Liu Haiyan Sun |
| author_sort | Zijun Ouyang |
| collection | DOAJ |
| description | Excessive consumption of acetaminophen (APAP) has emerged as the primary culprit behind drug-induced liver injury (DILI), with N-acetylcysteine serving as the principal antidote. However, use of N-acetylcysteine is limited to the early stages of APAP-induced DILI and may cause adverse side effects. Consequently, it is imperative to explore alternative therapeutic approaches to alleviate APAP-induced liver toxicity. In this study the mechanisms underlying the protective role of epigallocatechin gallate (EGCG) in DILI were determined. Our findings revealed that EGCG inhibited NEDD8, thus stabilizing HUWE1, a crucial E3 ubiquitin ligase involved in protein degradation. HUWE1 binds and degrades TFR1, a protein essential for cellular iron uptake and inhibits ferroptosis. By stabilizing HUWE1 and degrading TFR1, EGCG suppressed ferroptosis and ameliorated APAP-induced liver injury. Our results highlight the therapeutic potential of EGCG in mitigating DILI through regulation of HUWE1 and ferroptosis, which offers a promising approach for the treatment of DILI. |
| format | Article |
| id | doaj-art-dcf78eda6164477896d2b787cc201960 |
| institution | Kabale University |
| issn | 2737-7946 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Compuscript Ltd |
| record_format | Article |
| series | Acta Materia Medica |
| spelling | doaj-art-dcf78eda6164477896d2b787cc2019602025-08-20T03:28:10ZengCompuscript LtdActa Materia Medica2737-79462025-01-014220721510.15212/AMM-2024-0087EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitroZijun OuyangTao ZhangMengting LiuFufu LiHui GuoYanhui LiJieyu ChenFeiyang WangYang SunDong LiuHaiyan SunExcessive consumption of acetaminophen (APAP) has emerged as the primary culprit behind drug-induced liver injury (DILI), with N-acetylcysteine serving as the principal antidote. However, use of N-acetylcysteine is limited to the early stages of APAP-induced DILI and may cause adverse side effects. Consequently, it is imperative to explore alternative therapeutic approaches to alleviate APAP-induced liver toxicity. In this study the mechanisms underlying the protective role of epigallocatechin gallate (EGCG) in DILI were determined. Our findings revealed that EGCG inhibited NEDD8, thus stabilizing HUWE1, a crucial E3 ubiquitin ligase involved in protein degradation. HUWE1 binds and degrades TFR1, a protein essential for cellular iron uptake and inhibits ferroptosis. By stabilizing HUWE1 and degrading TFR1, EGCG suppressed ferroptosis and ameliorated APAP-induced liver injury. Our results highlight the therapeutic potential of EGCG in mitigating DILI through regulation of HUWE1 and ferroptosis, which offers a promising approach for the treatment of DILI.https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0087 |
| spellingShingle | Zijun Ouyang Tao Zhang Mengting Liu Fufu Li Hui Guo Yanhui Li Jieyu Chen Feiyang Wang Yang Sun Dong Liu Haiyan Sun EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro Acta Materia Medica |
| title | EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro |
| title_full | EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro |
| title_fullStr | EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro |
| title_full_unstemmed | EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro |
| title_short | EGCG inhibits ferroptosis to ameliorate APAP-induced liver injury by suppressing NEDD8 and stabilizing HUWE1 in vivo and in vitro |
| title_sort | egcg inhibits ferroptosis to ameliorate apap induced liver injury by suppressing nedd8 and stabilizing huwe1 in vivo and in vitro |
| url | https://www.scienceopen.com/hosted-document?doi=10.15212/AMM-2024-0087 |
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