Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway
Abstract Objective Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear. Methods An in vitro DCM model was established using H9C2 cells induced with high glucose (H...
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| Format: | Article |
| Language: | English |
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BMC
2023-07-01
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| Series: | Journal of Cardiothoracic Surgery |
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| Online Access: | https://doi.org/10.1186/s13019-023-02300-7 |
| _version_ | 1797778739663208448 |
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| author | Fan Li Zhenfei Hu Yidan Huang Haiting Zhan |
| author_facet | Fan Li Zhenfei Hu Yidan Huang Haiting Zhan |
| author_sort | Fan Li |
| collection | DOAJ |
| description | Abstract Objective Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear. Methods An in vitro DCM model was established using H9C2 cells induced with high glucose (HG) and treated with DEX at varying doses and a nuclear factor erythroid 2-realated factor 2 (Nrf2) specific inhibitor ML385. Cell viability was evaluated using the MTT method after treatment with DEX or mannitol (MAN), and the dosage of DEX used in subsequent experimentation was determined. The effects of HG-induced high osmotic pressure were assessed using MAN as a control. Cell apoptosis was evaluated using flow cytometry. Protein levels of Bcl2, Bax, nuclear Nrf2, and glutathione peroxidase 4 (GPX4) were measured using Western blot. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, Fe2+ concentration and reactive oxygen species (ROS) levels were measured using corresponding kits and dichlorodihydrofluorescein diacetate, respectively. Results Treatment with DEX or MAN had no effect on H9C2 cell viability. HG induction reduced H9C2 cell viability, increased cell apoptosis, upregulated levels of Bax, Fe2+, MDA, and ROS, and downregulated Bcl2 protein levels, SOD activity, and protein levels of nuclear Nrf2 and GPX4. DEX inhibited HG-induced H9C2 cell apoptosis, promoted Nrf2 nuclear translocation, and activated the Nrf2/GPX4 pathway. Inhibition of Nrf2 partially reversed the protective effects of DEX against HG-evoked H9C2 cell injury. Conclusion Our findings demonstrate that DEX attenuates HG-induced cardiomyocyte injury by inhibiting ferroptosis through the Nrf2/GPX4 pathway, providing potential therapeutic targets for DCM treatment. |
| first_indexed | 2024-03-12T23:21:52Z |
| format | Article |
| id | doaj.art-fd49008edde248c79e012c84ce094d13 |
| institution | Directory Open Access Journal |
| issn | 1749-8090 |
| language | English |
| last_indexed | 2024-03-12T23:21:52Z |
| publishDate | 2023-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Cardiothoracic Surgery |
| spelling | doaj.art-fd49008edde248c79e012c84ce094d132023-07-16T11:27:34ZengBMCJournal of Cardiothoracic Surgery1749-80902023-07-011811810.1186/s13019-023-02300-7Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathwayFan Li0Zhenfei Hu1Yidan Huang2Haiting Zhan3Department of Anesthesiology, First Afiliated Hospital of Xinjiang Medical University, Xinjiang Perioperative Organ Protection Laboratory (XJDX1411)Department of Anesthesiology, First Afiliated Hospital of Xinjiang Medical University, Xinjiang Perioperative Organ Protection Laboratory (XJDX1411)Department of Anesthesiology, First Afiliated Hospital of Xinjiang Medical University, Xinjiang Perioperative Organ Protection Laboratory (XJDX1411)Department of Anesthesiology, First Afiliated Hospital of Xinjiang Medical University, Xinjiang Perioperative Organ Protection Laboratory (XJDX1411)Abstract Objective Dexmedetomidine (DEX) has been shown to have anti-apoptotic effects in diabetes mellitus, but its role in mitigating diabetic cardiomyopathy (DCM) through ferroptosis regulation is unclear. Methods An in vitro DCM model was established using H9C2 cells induced with high glucose (HG) and treated with DEX at varying doses and a nuclear factor erythroid 2-realated factor 2 (Nrf2) specific inhibitor ML385. Cell viability was evaluated using the MTT method after treatment with DEX or mannitol (MAN), and the dosage of DEX used in subsequent experimentation was determined. The effects of HG-induced high osmotic pressure were assessed using MAN as a control. Cell apoptosis was evaluated using flow cytometry. Protein levels of Bcl2, Bax, nuclear Nrf2, and glutathione peroxidase 4 (GPX4) were measured using Western blot. Superoxide dismutase (SOD) activity, malondialdehyde (MDA) levels, Fe2+ concentration and reactive oxygen species (ROS) levels were measured using corresponding kits and dichlorodihydrofluorescein diacetate, respectively. Results Treatment with DEX or MAN had no effect on H9C2 cell viability. HG induction reduced H9C2 cell viability, increased cell apoptosis, upregulated levels of Bax, Fe2+, MDA, and ROS, and downregulated Bcl2 protein levels, SOD activity, and protein levels of nuclear Nrf2 and GPX4. DEX inhibited HG-induced H9C2 cell apoptosis, promoted Nrf2 nuclear translocation, and activated the Nrf2/GPX4 pathway. Inhibition of Nrf2 partially reversed the protective effects of DEX against HG-evoked H9C2 cell injury. Conclusion Our findings demonstrate that DEX attenuates HG-induced cardiomyocyte injury by inhibiting ferroptosis through the Nrf2/GPX4 pathway, providing potential therapeutic targets for DCM treatment.https://doi.org/10.1186/s13019-023-02300-7Diabetic cardiomyopathyDexmedetomidineFerroptosisNrf2/GPX4 pathwayOxidative stressH9C2 cells |
| spellingShingle | Fan Li Zhenfei Hu Yidan Huang Haiting Zhan Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway Journal of Cardiothoracic Surgery Diabetic cardiomyopathy Dexmedetomidine Ferroptosis Nrf2/GPX4 pathway Oxidative stress H9C2 cells |
| title | Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway |
| title_full | Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway |
| title_fullStr | Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway |
| title_full_unstemmed | Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway |
| title_short | Dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the Nrf2/GPX4 pathway |
| title_sort | dexmedetomidine ameliorates diabetic cardiomyopathy by inhibiting ferroptosis through the nrf2 gpx4 pathway |
| topic | Diabetic cardiomyopathy Dexmedetomidine Ferroptosis Nrf2/GPX4 pathway Oxidative stress H9C2 cells |
| url | https://doi.org/10.1186/s13019-023-02300-7 |
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