Early morphological changes in cardiac mitochondria after subcutaneous administration of trastuzumab in rabbits: possible prevention with oral selenium supplementation
| Autor: | Ling Wang, Hemasri Tokala, Brian J Grondahl, Michael Kehdi, Heather Laird-Fick, Augusta Pelosi, Samanjit Kaur Kandola |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Antioxidant Time Factors Heart Diseases medicine.medical_treatment Lymphocyte Injections Subcutaneous Administration Oral Pilot Projects 030204 cardiovascular system & hematology Mitochondrion Pharmacology Mitochondria Heart Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Antineoplastic Agents Immunological Sodium Selenite Trastuzumab Edema medicine Animals Myocytes Cardiac skin and connective tissue diseases Cardiotoxicity business.industry General Medicine 030104 developmental biology medicine.anatomical_structure Dietary Supplements Histopathology Rabbits medicine.symptom Cardiology and Cardiovascular Medicine business Myofibril medicine.drug |
| Zdroj: | Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 44 |
| ISSN: | 1879-1336 |
| Popis: | Trastuzumab-mediated cardiotoxicity poses a significant challenge in the treatment of human epidermal growth factor receptor 2-positive breast cancer. To understand the underlying mechanisms, we conducted experiments to determine ultrastructural changes of rabbit cardiac tissue under different experimental conditions, including differing doses of trastuzumab and supplementation with oral sodium selenite, an antioxidant. Histopathology revealed lymphocyte and macrophage infiltration in myocardium of rabbits receiving four doses of trastuzumab. Transmission electron microscopy showed substantial changes with trastuzumab, including edema with separation of myofibril bundles and rupture of sarcomeres. Within mitochondria, edema resulted in disorganization of the cristae. Some mitochondria exhibited eccentric projections of their membranes with disruption of both inner and outer membranes. These changes were seen to a lesser extent in rabbits who received oral sodium selenite prior to trastuzumab. Selenium is integral to functioning of mitochondrial glutathione peroxidases, important antioxidants that also maintain membrane integrity. If mitochondria are disrupted as part of trastuzumab cardiac toxicity, selenium supplementation might be an important therapeutic or preventive consideration. Larger studies to explore this hypothesis are warranted. |
| Databáze: | OpenAIRE |
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