Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation
Objective: Fine particulate matter (PM2.5) is a source of pollution worldwide, that causes inflammation and liver fibrosis. Melatonin, as the predominant hormone secreted by the pineal gland, can inhibit PM2.5-induced lung injury by activating nuclear factor erythroid 2-related factor 2 (Nrf2) to in...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323012216 |
| _version_ | 1797435801816006656 |
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| author | Laiyu Zhu Qi Zhang Cong Hua Xinxin Ci |
| author_facet | Laiyu Zhu Qi Zhang Cong Hua Xinxin Ci |
| author_sort | Laiyu Zhu |
| collection | DOAJ |
| description | Objective: Fine particulate matter (PM2.5) is a source of pollution worldwide, that causes inflammation and liver fibrosis. Melatonin, as the predominant hormone secreted by the pineal gland, can inhibit PM2.5-induced lung injury by activating nuclear factor erythroid 2-related factor 2 (Nrf2) to inhibit ferroptosis. However, the possible role of melatonin in PM2.5-induced liver damage remains unclear. Experimental approach: In vitro, the effects of melatonin on PM2.5-induced oxidative stress and LX-2 cell activation were examined. In vivo, a PM2.5-induced inflammation and liver fibrosis mouse model was used to evaluate the hepatoprotective effect of melatonin. Results: In vitro, melatonin induced the expression of Nrf2 and its downstream genes and inhibited PM2.5-induced reactive oxygen species (ROS) production and mitochondrial damage. Melatonin also ameliorated the PM2.5-induced oxidative stress and fibrogenic marker upregulation. However, the antifibrotic effect of melatonin was abolished in siNrf2-treated LX-2 cells. In vivo, we observed mitochondrial abnormalities and mitochondrial fragmentation, which were accompanied by increased PTEN-induced kinase 1 (PINK1) and Parkin expression, in PM2.5-treated mouse hepatocytes. These changes were partially reversed by melatonin. In addition, melatonin activated the Nrf2 signaling pathway and protected against PM2.5-induced oxidative stress. Furthermore, melatonin alleviated inflammation and liver fibrosis. Moreover, Nrf2-KO mice exhibited more severe inflammation and liver fibrosis after PM2.5 exposure than wild-type mice, and the protective effect of melatonin on PM2.5- treated Nrf2-KO mice was greatly compromised. Conclusion: These data suggest that melatonin effectively inhibits PM2.5-induced liver fibrosis by activating Nrf2 and inhibiting ROS-mediated mitophagy and inflammation. |
| first_indexed | 2024-03-09T10:53:20Z |
| format | Article |
| id | doaj.art-5e150ae606074b87be7dbb7fcfa3e385 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-09T10:53:20Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-5e150ae606074b87be7dbb7fcfa3e3852023-12-01T05:00:34ZengElsevierEcotoxicology and Environmental Safety0147-65132023-12-01268115717Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activationLaiyu Zhu0Qi Zhang1Cong Hua2Xinxin Ci3Institute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, ChinaDepartment of Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130001, ChinaDepartment of Surgical Neuro-oncology, The First Hospital of Jilin University, Changchun, Jilin 130001, ChinaInstitute of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin 130001, China; Correspondence to: The First Hospital of Jilin University, Dongminzhu road 519, Changchun, Jilin 130001, China.Objective: Fine particulate matter (PM2.5) is a source of pollution worldwide, that causes inflammation and liver fibrosis. Melatonin, as the predominant hormone secreted by the pineal gland, can inhibit PM2.5-induced lung injury by activating nuclear factor erythroid 2-related factor 2 (Nrf2) to inhibit ferroptosis. However, the possible role of melatonin in PM2.5-induced liver damage remains unclear. Experimental approach: In vitro, the effects of melatonin on PM2.5-induced oxidative stress and LX-2 cell activation were examined. In vivo, a PM2.5-induced inflammation and liver fibrosis mouse model was used to evaluate the hepatoprotective effect of melatonin. Results: In vitro, melatonin induced the expression of Nrf2 and its downstream genes and inhibited PM2.5-induced reactive oxygen species (ROS) production and mitochondrial damage. Melatonin also ameliorated the PM2.5-induced oxidative stress and fibrogenic marker upregulation. However, the antifibrotic effect of melatonin was abolished in siNrf2-treated LX-2 cells. In vivo, we observed mitochondrial abnormalities and mitochondrial fragmentation, which were accompanied by increased PTEN-induced kinase 1 (PINK1) and Parkin expression, in PM2.5-treated mouse hepatocytes. These changes were partially reversed by melatonin. In addition, melatonin activated the Nrf2 signaling pathway and protected against PM2.5-induced oxidative stress. Furthermore, melatonin alleviated inflammation and liver fibrosis. Moreover, Nrf2-KO mice exhibited more severe inflammation and liver fibrosis after PM2.5 exposure than wild-type mice, and the protective effect of melatonin on PM2.5- treated Nrf2-KO mice was greatly compromised. Conclusion: These data suggest that melatonin effectively inhibits PM2.5-induced liver fibrosis by activating Nrf2 and inhibiting ROS-mediated mitophagy and inflammation.http://www.sciencedirect.com/science/article/pii/S0147651323012216MelatoninPM2.5Liver FibrosisNrf2MitophagyInflammation |
| spellingShingle | Laiyu Zhu Qi Zhang Cong Hua Xinxin Ci Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation Ecotoxicology and Environmental Safety Melatonin PM2.5 Liver Fibrosis Nrf2 Mitophagy Inflammation |
| title | Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation |
| title_full | Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation |
| title_fullStr | Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation |
| title_full_unstemmed | Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation |
| title_short | Melatonin alleviates particulate matter-induced liver fibrosis by inhibiting ROS-mediated mitophagy and inflammation via Nrf2 activation |
| title_sort | melatonin alleviates particulate matter induced liver fibrosis by inhibiting ros mediated mitophagy and inflammation via nrf2 activation |
| topic | Melatonin PM2.5 Liver Fibrosis Nrf2 Mitophagy Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323012216 |
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