4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice
Acetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-in...
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.00653/full |
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| author | Hongqiong Zhao Zhihui Jiang Xuemei Chang Huiting Xue Huiting Xue Wumaierjiang Yahefu Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang |
| author_facet | Hongqiong Zhao Zhihui Jiang Xuemei Chang Huiting Xue Huiting Xue Wumaierjiang Yahefu Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang |
| author_sort | Hongqiong Zhao |
| collection | DOAJ |
| description | Acetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-induced hepatotoxicity, as well as the putative mechanisms involved. Mice were treated with 4-HPA (6, 12, or 25 mg/kg) for 3 days, 1 h after the last administration of 4-HPA, a single dose of APAP was intraperitoneally infused for mice. APAP caused a remarkable increase of oxidative stress markers, peroxynitrite formation, and fewer activated phase II enzymes. 4-HPA increased Nrf2 translocation to the nucleus and enhanced the activity of phase II and antioxidant enzymes, and could thereby ameliorate APAP-induced liver injury. Studies reveal that 4-HPA, as an active area of bioactive dietary constituents, could protect the liver against APAP-induced injury, implying that 4-HPA could be a new promising strategy and natural hepatoprotective drug. |
| first_indexed | 2024-12-10T18:25:57Z |
| format | Article |
| id | doaj.art-ae81da5ebfff4249b2046b2ec18d891d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T18:25:57Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-ae81da5ebfff4249b2046b2ec18d891d2022-12-22T01:38:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.006533423514-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in MiceHongqiong Zhao0Zhihui Jiang1Xuemei Chang2Huiting Xue3Huiting Xue4Wumaierjiang Yahefu5Xiaoying Zhang6Xiaoying Zhang7Xiaoying Zhang8Xiaoying Zhang9College of Veterinary Medicine, Xinjiang Agricultural University, Xinjiang, ChinaResearch Center of Modern Biotechnology, Anyang Institute of Technology, Anyang, ChinaCollege of Veterinary Medicine, Xinjiang Agricultural University, Xinjiang, ChinaCollege of Veterinary Medicine, Xinjiang Agricultural University, Xinjiang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaCollege of Veterinary Medicine, Xinjiang Agricultural University, Xinjiang, ChinaCollege of Veterinary Medicine, Xinjiang Agricultural University, Xinjiang, ChinaResearch Center of Modern Biotechnology, Anyang Institute of Technology, Anyang, ChinaCollege of Veterinary Medicine, Northwest A&F University, Yangling, ChinaDepartment of Biology, Centre of Molecular and Environmental Biology, University of Minho, Braga, PortugalAcetaminophen (APAP) overdose is the principal cause of drug-induced acute liver failure. 4-hydroxyphenylacetic acid (4-HPA), a major microbiota-derived metabolite of polyphenols, is involved in the antioxidative action. This study seeks to investigate the ability of 4-HPA to protect against APAP-induced hepatotoxicity, as well as the putative mechanisms involved. Mice were treated with 4-HPA (6, 12, or 25 mg/kg) for 3 days, 1 h after the last administration of 4-HPA, a single dose of APAP was intraperitoneally infused for mice. APAP caused a remarkable increase of oxidative stress markers, peroxynitrite formation, and fewer activated phase II enzymes. 4-HPA increased Nrf2 translocation to the nucleus and enhanced the activity of phase II and antioxidant enzymes, and could thereby ameliorate APAP-induced liver injury. Studies reveal that 4-HPA, as an active area of bioactive dietary constituents, could protect the liver against APAP-induced injury, implying that 4-HPA could be a new promising strategy and natural hepatoprotective drug.https://www.frontiersin.org/article/10.3389/fphar.2018.00653/fullpolyphenols4-hydroxyphenylacetic acid 4-HPAacetaminophen APAPhepatotoxicityoxidative stressnuclear factor erythroid 2-related factor |
| spellingShingle | Hongqiong Zhao Zhihui Jiang Xuemei Chang Huiting Xue Huiting Xue Wumaierjiang Yahefu Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang Xiaoying Zhang 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice Frontiers in Pharmacology polyphenols 4-hydroxyphenylacetic acid 4-HPA acetaminophen APAP hepatotoxicity oxidative stress nuclear factor erythroid 2-related factor |
| title | 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice |
| title_full | 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice |
| title_fullStr | 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice |
| title_full_unstemmed | 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice |
| title_short | 4-Hydroxyphenylacetic Acid Prevents Acute APAP-Induced Liver Injury by Increasing Phase II and Antioxidant Enzymes in Mice |
| title_sort | 4 hydroxyphenylacetic acid prevents acute apap induced liver injury by increasing phase ii and antioxidant enzymes in mice |
| topic | polyphenols 4-hydroxyphenylacetic acid 4-HPA acetaminophen APAP hepatotoxicity oxidative stress nuclear factor erythroid 2-related factor |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.00653/full |
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