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Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway
Oxidative stress induced by chemotherapeutic agents causes hepatotoxicity. 5-Fluorouracil (5-FU) has been found to have a variety of side effects, but its toxic effect on the liver and the mechanism are still unclear. Angelica polysaccharide (ASP), the main active ingredient of Dang Gui, has antioxi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415481/ https://www.ncbi.nlm.nih.gov/pubmed/34485154 http://dx.doi.org/10.3389/fonc.2021.720620 |
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author | Zeng, Di Wang, Yaping Chen, Yi Li, Danyang Li, Guoli Xiao, Hanxianzhi Hou, Jiyin Wang, Ziling Hu, Ling Wang, Lu Li, Jing |
author_facet | Zeng, Di Wang, Yaping Chen, Yi Li, Danyang Li, Guoli Xiao, Hanxianzhi Hou, Jiyin Wang, Ziling Hu, Ling Wang, Lu Li, Jing |
author_sort | Zeng, Di |
collection | PubMed |
description | Oxidative stress induced by chemotherapeutic agents causes hepatotoxicity. 5-Fluorouracil (5-FU) has been found to have a variety of side effects, but its toxic effect on the liver and the mechanism are still unclear. Angelica polysaccharide (ASP), the main active ingredient of Dang Gui, has antioxidative stress effects. In this study, we investigated the antagonistic effects of ASP on 5-FU-induced injury in the mouse liver and human normal liver cell line MIHA and the possible mechanism. Our results show that ASP inhibited 5-FU-induced the decrease in Bcl-2 protein and the increase in Bax protein. ASP alleviated 5-FU-induced the increase in alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) content; hepatic steatosis; and liver fibrosis. ASP restored 5-FU-induced swelling of mitochondria and the endoplasmic reticulum. 5-FU promoted the expression of Keap1 and increased the binding to NF-E2-related factor 2 (Nrf2) to reduce the nuclear translocation of Nrf2, thereby weakening the transcriptional activity of Nrf2 to inhibit the expression of HO-1; reducing the activity of GSH, SOD, and CAT to increase ROS content; and aggravating DNA damage (indicated by the increase in 8-OHdG). However, ASP reversed these reactions. In conclusion, ASP attenuated the 5-FU-induced Nrf2 pathway barrier to reduce oxidative stress injury and thereby inhibit the disorder of lipid anabolism and apoptosis. The study provides a new protectant for reducing the hepatic toxicity caused by 5-FU and a novel target for treating the liver injury. |
format | Online Article Text |
id | pubmed-8415481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84154812021-09-04 Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway Zeng, Di Wang, Yaping Chen, Yi Li, Danyang Li, Guoli Xiao, Hanxianzhi Hou, Jiyin Wang, Ziling Hu, Ling Wang, Lu Li, Jing Front Oncol Oncology Oxidative stress induced by chemotherapeutic agents causes hepatotoxicity. 5-Fluorouracil (5-FU) has been found to have a variety of side effects, but its toxic effect on the liver and the mechanism are still unclear. Angelica polysaccharide (ASP), the main active ingredient of Dang Gui, has antioxidative stress effects. In this study, we investigated the antagonistic effects of ASP on 5-FU-induced injury in the mouse liver and human normal liver cell line MIHA and the possible mechanism. Our results show that ASP inhibited 5-FU-induced the decrease in Bcl-2 protein and the increase in Bax protein. ASP alleviated 5-FU-induced the increase in alanine aminotransferase (ALT), triglyceride (TG), and aspartate aminotransferase (AST) content; hepatic steatosis; and liver fibrosis. ASP restored 5-FU-induced swelling of mitochondria and the endoplasmic reticulum. 5-FU promoted the expression of Keap1 and increased the binding to NF-E2-related factor 2 (Nrf2) to reduce the nuclear translocation of Nrf2, thereby weakening the transcriptional activity of Nrf2 to inhibit the expression of HO-1; reducing the activity of GSH, SOD, and CAT to increase ROS content; and aggravating DNA damage (indicated by the increase in 8-OHdG). However, ASP reversed these reactions. In conclusion, ASP attenuated the 5-FU-induced Nrf2 pathway barrier to reduce oxidative stress injury and thereby inhibit the disorder of lipid anabolism and apoptosis. The study provides a new protectant for reducing the hepatic toxicity caused by 5-FU and a novel target for treating the liver injury. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415481/ /pubmed/34485154 http://dx.doi.org/10.3389/fonc.2021.720620 Text en Copyright © 2021 Zeng, Wang, Chen, Li, Li, Xiao, Hou, Wang, Hu, Wang and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zeng, Di Wang, Yaping Chen, Yi Li, Danyang Li, Guoli Xiao, Hanxianzhi Hou, Jiyin Wang, Ziling Hu, Ling Wang, Lu Li, Jing Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title | Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title_full | Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title_fullStr | Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title_full_unstemmed | Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title_short | Angelica Polysaccharide Antagonizes 5-FU-Induced Oxidative Stress Injury to Reduce Apoptosis in the Liver Through Nrf2 Pathway |
title_sort | angelica polysaccharide antagonizes 5-fu-induced oxidative stress injury to reduce apoptosis in the liver through nrf2 pathway |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415481/ https://www.ncbi.nlm.nih.gov/pubmed/34485154 http://dx.doi.org/10.3389/fonc.2021.720620 |
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