Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: Role of endoplasmic reticulum stress
| العنوان: | Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: Role of endoplasmic reticulum stress |
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| المؤلفون: | Heng Ma, Jun Ren, Rui Guo, Kyla R Jones, Peisheng Xu, Youqing Shen |
| المصدر: | Clinical and Experimental Pharmacology and Physiology. 37:460-465 |
| بيانات النشر: | Wiley, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Male, Contraction (grammar), Physiology, Antineoplastic Agents, Apoptosis, Mitochondrion, Biology, Pharmacology, Endoplasmic Reticulum, Cardiotoxins, Mitochondria, Heart, Mice, Stress, Physiological, Physiology (medical), medicine, Animals, Myocytes, Cardiac, Cell Shape, Cells, Cultured, Membrane Potential, Mitochondrial, Cisplatin, Cardiotoxicity, TUNEL assay, Caspase 3, Myocardium, Endoplasmic reticulum, Hemodynamics, Heart, Organ Size, Anatomy, Myocardial Contraction, Mice, Inbred C57BL, Depression, Chemical, Unfolded protein response, medicine.drug |
| الوصف: | 1. Cisplatin is a potent chemotherapeutic agent with broad-spectrum antineoplastic activity against various types of tumours. However, a major factor limiting treatment with cisplatin is its acute and cumulative cardiotoxicity. The aim of the present study was to explore the effect of cisplatin on myocardial contractile function and the possible underlying cellular mechanisms. 2. C57 mice were treated with cisplatin (10 mg/kg per day, i.v.) or vehicle (0.9% NaCl) for 1 week and myocardial function was assessed using the Langendorff and cardiomyocyte edge-detection systems. Transmission electron microscopy, mitochondrial membrane potential, indices of endoplasmic reticulum (ER) stress and caspase 3 activity were evaluated. 3. Cisplatin-treated mice developed myocardial contractile dysfunction, as evidenced by a reduction in left ventricular developed pressure (LVDP) and the first derivative of LVDP (+/-dP/dt). Cisplatin treatment significantly prolonged time to 90% relengthening, depressed peak shortening, maximal velocity of shortening/relengthening (+/-dL/dt) and augmented the frequency-elicited depression in peak shortening. The JC-1 fluorescent assay demonstrated that cispatin-induced cardiac dysfunction was associated with mitochondrial membrane depolarization. Transmission electron microscopy revealed that cisplatin induces ultrastructural abnormalities of the mitochondria. Following cisplatin treatment, cardiomyocytes show activation of the ER stress response, increased caspase 3 activity and increased terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) staining. 4. The data indicate that cisplatin is cardiotoxic and may lead to left ventricular dysfunction and depressed cardiomyocyte contraction associated with mitochondrial abnormalities, enhanced ER stress and apoptosis. This work should shed some light on the management of cisplatin-induced cardiac injury. |
| تدمد: | 1440-1681 0305-1870 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d21472bd8d2f95fd1117f3a53fc4459 https://doi.org/10.1111/j.1440-1681.2009.05323.x |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....7d21472bd8d2f95fd1117f3a53fc4459 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14401681 03051870 |
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