Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms
文献类型：期刊论文
| 作者 | Berlanga-Acosta, Jorge3; Cibrian, Danay3; Valiente-Mustelier, Juan2; Suarez-Alba, Jose3; Garcia-Ojalvo, Ariana3; Falcon-Cama, Viviana3; Jiang, Baohong1 ; Wang, Linlin1; Guillen-Nieto, Gerardo3
|
| 刊名 | FRONTIERS IN PHARMACOLOGY
 |
| 出版日期 | 2024-05-30 |
| 卷号 | 15页码:17 |
| 关键词 | doxorubicin dilated cardiomyopathy GHRP-6 heart failure ventricular dilation |
| DOI | 10.3389/fphar.2024.1402138 |
| 通讯作者 | Berlanga-Acosta, Jorge(jorge.berlanga@cigb.edu.cu) |
| 英文摘要 | Introduction: Dilated cardiomyopathy (DCM) is a fatal myocardial condition with ventricular structural changes and functional deficits, leading to systolic dysfunction and heart failure (HF). DCM is a frequent complication in oncologic patients receiving Doxorubicin (Dox). Dox is a highly cardiotoxic drug, whereas its damaging spectrum affects most of the organs by multiple pathogenic cascades. Experimentally reproduced DCM/HF through Dox administrations has shed light on the pathogenic drivers of cardiotoxicity. Growth hormone (GH) releasing peptide 6 (GHRP-6) is a GH secretagogue with expanding and promising cardioprotective pharmacological properties. Here we examined whether GHRP-6 administration concomitant to Dox prevented the onset of DCM/HF and multiple organs damages in otherwise healthy rats.Methods: Myocardial changes were sequentially evaluated by transthoracic echocardiography. Autopsy was conducted at the end of the administration period when ventricular dilation was established. Semiquantitative histopathologic study included heart and other internal organs samples. Myocardial tissue fragments were also addressed for electron microscopy study, and characterization of the transcriptional expression ratio between Bcl-2 and Bax. Serum samples were destined for REDOX system balance assessment.Results and discussion: GHRP-6 administration in parallel to Dox prevented myocardial fibers consumption and ventricular dilation, accounting for an effective preservation of the LV systolic function. GHRP-6 also attenuated extracardiac toxicity preserving epithelial organs integrity, inhibiting interstitial fibrosis, and ultimately reducing morbidity and mortality. Mechanistically, GHRP-6 proved to sustain cellular antioxidant defense, upregulate prosurvival gene Bcl-2, and preserve cardiomyocyte mitochondrial integrity. These evidences contribute to pave potential avenues for the clinical use of GHRP-6 in Dox-treated subjects. |
| WOS关键词 | LEFT-VENTRICULAR DYSFUNCTION ; DES-ACYL GHRELIN ; OXIDATIVE STRESS ; INDUCED CARDIOTOXICITY ; CELL-DEATH ; RAT MODEL ; APOPTOSIS ; LIVER ; CD36 ; EXPRESSION |
| 资助项目 | Funds for this study corresponded to biomedical research area of the Center for Genetic Engineering and Biotechnology[3051-280] ; National Key R&D Program of China[2021YFE0111300] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:001244826500001 |
| 出版者 | FRONTIERS MEDIA SA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311413]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Berlanga-Acosta, Jorge |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China 2.Inst Cardiol & Cardiovasc Surg, Havana, Cuba 3.Ctr Genet Engn & Biotechnol, Playa, Cuba |
| 推荐引用方式 GB/T 7714 | Berlanga-Acosta, Jorge,Cibrian, Danay,Valiente-Mustelier, Juan,et al. Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms[J]. FRONTIERS IN PHARMACOLOGY,2024,15:17. |
| APA | Berlanga-Acosta, Jorge.,Cibrian, Danay.,Valiente-Mustelier, Juan.,Suarez-Alba, Jose.,Garcia-Ojalvo, Ariana.,...&Guillen-Nieto, Gerardo.(2024).Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms.FRONTIERS IN PHARMACOLOGY,15,17. |
| MLA | Berlanga-Acosta, Jorge,et al."Growth hormone releasing peptide-6 (GHRP-6) prevents doxorubicin-induced myocardial and extra-myocardial damages by activating prosurvival mechanisms".FRONTIERS IN PHARMACOLOGY 15(2024):17. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。