Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis
Adriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstra...
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| Format: | Article |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.812594/full |
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| author | Lu-Yun Qin Peng Guan Peng Guan Jian-Xin Wang Yu Chen Ya-Shuo Zhao Sheng-Chang Yang Ya-Jing Guo Na Wang Na Wang En-Sheng Ji En-Sheng Ji |
| author_facet | Lu-Yun Qin Peng Guan Peng Guan Jian-Xin Wang Yu Chen Ya-Shuo Zhao Sheng-Chang Yang Ya-Jing Guo Na Wang Na Wang En-Sheng Ji En-Sheng Ji |
| author_sort | Lu-Yun Qin |
| collection | DOAJ |
| description | Adriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstrated that ASIV significantly ameliorated kidney injury, improved renal dysfunction, reduced oxidative stress, alleviated iron accumulation, and inhibited the induction of ferroptosis by ADR. ASIV also rescued the intracellular levels of nuclear factor-erythroid-2-related factor 2 (Nrf2) and promoted nuclear translocation of Nrf2. These protective effects of ASIV on renal injury might be attained through the ASIV-induced activation of the Pi3K/Akt signaling pathway. In vitro, the treatment of the HK-2 cells with fer-1 or deferoxamine mesylate obviously improved cell viability during Adriamycin administration. On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent. Moreover, ASIV lowered the expression of transferrin receptor 1 and divalent metal transporter 1 while enhancing the expression of ferropotin 1 and glutathione peroxidase 4 in ADR administrated cells, the effects of which were akin to those of deferoxamine mesylate. Furthermore, ASIV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways. |
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| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T00:57:42Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-154bb9ef36824b14be17f0b73a05701a2022-12-22T00:04:45ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-03-011310.3389/fphar.2022.812594812594Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via FerroptosisLu-Yun Qin0Peng Guan1Peng Guan2Jian-Xin Wang3Yu Chen4Ya-Shuo Zhao5Sheng-Chang Yang6Ya-Jing Guo7Na Wang8Na Wang9En-Sheng Ji10En-Sheng Ji11Department of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaCollege of Life Science, Hebei Normal University, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaHebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang, ChinaDepartment of Physiology, Hebei University of Chinese Medicine, Shijiazhuang, ChinaHebei Technology Innovation Center of TCM Formula Preparations, Shijiazhuang, ChinaAdriamycin (ADR) has been utilized to treat cancer for several decades. However, ADR-induced renal injury is one of the most common side effects accompanying ADR therapy. In the present study, we revealed that astragaloside IV (ASIV) was beneficial for renal injury caused by Adriamycin. We demonstrated that ASIV significantly ameliorated kidney injury, improved renal dysfunction, reduced oxidative stress, alleviated iron accumulation, and inhibited the induction of ferroptosis by ADR. ASIV also rescued the intracellular levels of nuclear factor-erythroid-2-related factor 2 (Nrf2) and promoted nuclear translocation of Nrf2. These protective effects of ASIV on renal injury might be attained through the ASIV-induced activation of the Pi3K/Akt signaling pathway. In vitro, the treatment of the HK-2 cells with fer-1 or deferoxamine mesylate obviously improved cell viability during Adriamycin administration. On the other hand, the protective role of ASIV can be abrogated by RSL3 to some extent. Moreover, ASIV lowered the expression of transferrin receptor 1 and divalent metal transporter 1 while enhancing the expression of ferropotin 1 and glutathione peroxidase 4 in ADR administrated cells, the effects of which were akin to those of deferoxamine mesylate. Furthermore, ASIV increased the phosphorylation of Pi3K, Akt, and the expression of Nrf2 and glutathione peroxidase 4 compared to HK-2 cells stimulated by ADR. However, Pi3K inhibitor LY294002 abrogated these activations. In conclusion, ferroptosis may involve in ADR-induced nephrotoxicity, and ASIV might protect nephrocytes against ADR-induced ferroptosis, perhaps via activations of the Pi3K/Akt and Nrf2 signaling pathways.https://www.frontiersin.org/articles/10.3389/fphar.2022.812594/fullkidneyastragaloside ⅣAdriamyciniron metabolismferroptosis |
| spellingShingle | Lu-Yun Qin Peng Guan Peng Guan Jian-Xin Wang Yu Chen Ya-Shuo Zhao Sheng-Chang Yang Ya-Jing Guo Na Wang Na Wang En-Sheng Ji En-Sheng Ji Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis Frontiers in Pharmacology kidney astragaloside Ⅳ Adriamycin iron metabolism ferroptosis |
| title | Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis |
| title_full | Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis |
| title_fullStr | Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis |
| title_full_unstemmed | Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis |
| title_short | Therapeutic Potential of Astragaloside IV Against Adriamycin-Induced Renal Damage in Rats via Ferroptosis |
| title_sort | therapeutic potential of astragaloside iv against adriamycin induced renal damage in rats via ferroptosis |
| topic | kidney astragaloside Ⅳ Adriamycin iron metabolism ferroptosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.812594/full |
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