Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice
Abstract Background Radiation‐induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), a derivative of artemisinin, affects oxidative stress, immunomodulation, and inflammation. It is uncert...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.1175 |
| _version_ | 1797292106092380160 |
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| author | Xin Ning Weidong Zhao Qiaoyuan Wu Cailan Wang Shixiong Liang |
| author_facet | Xin Ning Weidong Zhao Qiaoyuan Wu Cailan Wang Shixiong Liang |
| author_sort | Xin Ning |
| collection | DOAJ |
| description | Abstract Background Radiation‐induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), a derivative of artemisinin, affects oxidative stress, immunomodulation, and inflammation. It is uncertain whether DHA reduces RILI. In this work, we investigated the specific mechanisms of action of DHA in RILI. Methods Twenty‐four C57BL/6J mice were randomly divided into four groups of six mice each: Control group, irradiation (IR) group, IR + DHA group, and IR + DHA + Brusatol group. The IR group received no interventions along with radiation treatment. Mice were killed 30 days after the irradiation. Morphologic and pathologic changes in lung tissue were observed with hematoxylin and eosin staining. Detection of hydroxyproline levels for assessing the extent of pulmonary fibrosis. Tumor necrosis factor α (TNF‐α), transforming growth factor‐β (TGF‐β), glutathione peroxidase (GPX4), Nuclear factor erythroid 2‐related factor 2 (Nrf2), and heme oxygenase‐1 (HO‐1) expression in lung tissues were detected. In addition, mitochondrial ultrastructural changes in lung tissues were also observed, and the glutathione (GSH) content in lung tissues was assessed. Results DHA attenuated radiation‐induced pathological lung injury and hydroxyproline levels. Additionally, it decreased TNF‐α and TGF‐β after irradiation. DHA may additionally stimulate the Nrf2/HO‐1 pathway. DHA upregulated GPX4 and GSH levels and inhibited cellular ferroptosis. Brusatol reversed the inhibitory effect of DHA on ferroptosis and its protective effect on RILI. Conclusion DHA modulated the Nrf2/HO‐1 pathway to prevent cellular ferroptosis, which reduced RILI. Therefore, DHA could be a potential drug for the treatment of RILI. |
| first_indexed | 2024-03-07T19:46:57Z |
| format | Article |
| id | doaj.art-0070b580ab404cb7bc1632a46e0607a3 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-07T19:46:57Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-0070b580ab404cb7bc1632a46e0607a32024-02-28T18:18:31ZengWileyImmunity, Inflammation and Disease2050-45272024-02-01122n/an/a10.1002/iid3.1175Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in miceXin Ning0Weidong Zhao1Qiaoyuan Wu2Cailan Wang3Shixiong Liang4Department of Radiation Oncology Guangxi Medical University Cancer Hospital Nanning Guangxi Zhuang Autonomous Region ChinaDepartment of Radiation Oncology Guangxi Medical University Cancer Hospital Nanning Guangxi Zhuang Autonomous Region ChinaDepartment of Radiation Oncology Guangxi Medical University Cancer Hospital Nanning Guangxi Zhuang Autonomous Region ChinaDepartment of Radiation Oncology Guangxi Medical University Cancer Hospital Nanning Guangxi Zhuang Autonomous Region ChinaDepartment of Radiation Oncology Guangxi Medical University Cancer Hospital Nanning Guangxi Zhuang Autonomous Region ChinaAbstract Background Radiation‐induced lung injury (RILI) is a common consequence of thoracic radiation therapy that lacks effective preventative and treatment strategies. Dihydroartemisinin (DHA), a derivative of artemisinin, affects oxidative stress, immunomodulation, and inflammation. It is uncertain whether DHA reduces RILI. In this work, we investigated the specific mechanisms of action of DHA in RILI. Methods Twenty‐four C57BL/6J mice were randomly divided into four groups of six mice each: Control group, irradiation (IR) group, IR + DHA group, and IR + DHA + Brusatol group. The IR group received no interventions along with radiation treatment. Mice were killed 30 days after the irradiation. Morphologic and pathologic changes in lung tissue were observed with hematoxylin and eosin staining. Detection of hydroxyproline levels for assessing the extent of pulmonary fibrosis. Tumor necrosis factor α (TNF‐α), transforming growth factor‐β (TGF‐β), glutathione peroxidase (GPX4), Nuclear factor erythroid 2‐related factor 2 (Nrf2), and heme oxygenase‐1 (HO‐1) expression in lung tissues were detected. In addition, mitochondrial ultrastructural changes in lung tissues were also observed, and the glutathione (GSH) content in lung tissues was assessed. Results DHA attenuated radiation‐induced pathological lung injury and hydroxyproline levels. Additionally, it decreased TNF‐α and TGF‐β after irradiation. DHA may additionally stimulate the Nrf2/HO‐1 pathway. DHA upregulated GPX4 and GSH levels and inhibited cellular ferroptosis. Brusatol reversed the inhibitory effect of DHA on ferroptosis and its protective effect on RILI. Conclusion DHA modulated the Nrf2/HO‐1 pathway to prevent cellular ferroptosis, which reduced RILI. Therefore, DHA could be a potential drug for the treatment of RILI.https://doi.org/10.1002/iid3.1175dihydroartemisininferroptosisNrf2/HO‐1 pathwaysradiation‐induced lung injury |
| spellingShingle | Xin Ning Weidong Zhao Qiaoyuan Wu Cailan Wang Shixiong Liang Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice Immunity, Inflammation and Disease dihydroartemisinin ferroptosis Nrf2/HO‐1 pathways radiation‐induced lung injury |
| title | Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice |
| title_full | Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice |
| title_fullStr | Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice |
| title_full_unstemmed | Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice |
| title_short | Therapeutic potential of dihydroartemisinin in mitigating radiation‐induced lung injury: Inhibition of ferroptosis through Nrf2/HO‐1 pathways in mice |
| title_sort | therapeutic potential of dihydroartemisinin in mitigating radiation induced lung injury inhibition of ferroptosis through nrf2 ho 1 pathways in mice |
| topic | dihydroartemisinin ferroptosis Nrf2/HO‐1 pathways radiation‐induced lung injury |
| url | https://doi.org/10.1002/iid3.1175 |
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