Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice
The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses w...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Ecotoxicology and Environmental Safety |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323007832 |
| _version_ | 1797683216828596224 |
|---|---|
| author | Liang Xiong Jinyu Huang Chunmei Wu Qiong Yuan Sihui Wang Liye Zhu Zilu Li Ziyue Sun Yi Fang Weisong Li Gonghua Hu |
| author_facet | Liang Xiong Jinyu Huang Chunmei Wu Qiong Yuan Sihui Wang Liye Zhu Zilu Li Ziyue Sun Yi Fang Weisong Li Gonghua Hu |
| author_sort | Liang Xiong |
| collection | DOAJ |
| description | The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc− axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms. |
| first_indexed | 2024-03-12T00:11:21Z |
| format | Article |
| id | doaj.art-b2f34bae19d4403d8a61194aeccaecef |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-03-12T00:11:21Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-b2f34bae19d4403d8a61194aeccaecef2023-09-16T05:28:25ZengElsevierEcotoxicology and Environmental Safety0147-65132023-09-01263115279Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in miceLiang Xiong0Jinyu Huang1Chunmei Wu2Qiong Yuan3Sihui Wang4Liye Zhu5Zilu Li6Ziyue Sun7Yi Fang8Weisong Li9Gonghua Hu10Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Key Laboratory of Environment and Health of Ganzhou, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaSchool of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaSchool of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaSchool of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaSchool of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaDepartment of Pathology, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou 341000, Jiangxi, PR ChinaKey Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; School of Public Health and Health Management, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Key Laboratory of Environment and Health of Ganzhou, Gannan Medical University, Ganzhou 341000, Jiangxi, PR China; Correspondence to: School of Public Health and Health Management, Gannan Medical University, Yixueyuan Road, Ganzhou 341000, Jiangxi, PR China.The growing presence of yttrium (Y) in the environment raises concern regarding its safety and toxicity. However, limited toxicological data are available to determine cardiotoxicity of Y and its underlying mechanisms. In the present study, yttrium chloride (YCl3) intervention with different doses was performed in male Kunming mice for the toxicological evaluation of Y in the heart. After 28 days of intragastric administration, 500 mg/kg·bw YCl3 induces iron accumulation in cardiomyocytes, and triggers ferroptosis through the glutathione peroxidase 4 (GPX4)/glutathione (GSH)/system Xc− axis via the inhibition of Nrf2 signaling pathway. This process led to cardiac lipid peroxidation and inflammatory response. Further RNA sequencing transcriptome analysis found that many genes involved in ferroptosis and lipid metabolism-related pathways were enriched. The ferroptosis induced by YCl3 in cardiomyocytes ultimately caused cardiac injury and dysfunction in mice. Our findings assist in the elucidation of the potential subacute cardiotoxicity of Y3+ and its underlying mechanisms.http://www.sciencedirect.com/science/article/pii/S0147651323007832YttriumLipid peroxideInflammationFerroptosisCardiac dysfunction |
| spellingShingle | Liang Xiong Jinyu Huang Chunmei Wu Qiong Yuan Sihui Wang Liye Zhu Zilu Li Ziyue Sun Yi Fang Weisong Li Gonghua Hu Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice Ecotoxicology and Environmental Safety Yttrium Lipid peroxide Inflammation Ferroptosis Cardiac dysfunction |
| title | Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| title_full | Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| title_fullStr | Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| title_full_unstemmed | Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| title_short | Yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| title_sort | yttrium chloride induces ferroptosis in cardiomyocytes via iron accumulation and triggers cardiac lipid peroxidation and inflammation that cause heart adverse events in mice |
| topic | Yttrium Lipid peroxide Inflammation Ferroptosis Cardiac dysfunction |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323007832 |
| work_keys_str_mv | AT liangxiong yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT jinyuhuang yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT chunmeiwu yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT qiongyuan yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT sihuiwang yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT liyezhu yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT ziluli yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT ziyuesun yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT yifang yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT weisongli yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice AT gonghuahu yttriumchlorideinducesferroptosisincardiomyocytesviaironaccumulationandtriggerscardiaclipidperoxidationandinflammationthatcauseheartadverseeventsinmice |