| Autor: |
Guven C; Department of Biophysics, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey., Taskin E; Department of Physiology, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey., Aydın Ö; Department of Biology, Institute of Natural and Applied Sciences, Adıyaman University, Adıyaman, Turkey., Kaya ST; Department of Biology, Faculty of Science and Letters, Düzce University, Düzce, Turkey., Sevgiler Y; Department of Biology, Faculty of Science and Letters, Adıyaman University, Adıyaman, Turkey. |
| Jazyk: |
angličtina |
| Zdroj: |
Biotechnic & histochemistry : official publication of the Biological Stain Commission [Biotech Histochem] 2024 Apr; Vol. 99 (3), pp. 113-124. Date of Electronic Publication: 2024 Mar 05. |
| DOI: |
10.1080/10520295.2024.2324368 |
| Abstrakt: |
Doxorubicin (DOX)-induced cardiotoxicity is a well known clinical problem, and many investigations have been made of its possible amelioration. We have investigated whether diazoxide (DIA), an agonist at mitochondrial ATP-sensitive potassium channels (mitoK ATP ), could reverse DOX-induced apoptotic myocardial cell loss, in cultured rat cardiomyocytes. The role of certain proteins in this pathway was also studied. The rat cardiomyocyte cell line (H9c2) was treated with DOX, and also co-treated with DOX and DIA, for 24 h. Distribution of actin filaments, mitochondrial membrane potential, superoxide dismutase (SOD) activity, total oxidant and antioxidant status (TOS and TAS, respectively), and some protein expressions, were assessed. DOX significantly decreased SOD activity, increased ERK1/2 protein levels, and depolarised the mitochondrial membrane, while DIA co-treatment inhibited such changes. DIA co-treatment ameliorated DOX-induced cytoskeletal changes via F-actin distribution and mitoK ATP structure. Co-treatment also decreased ERK1/2 and cytochrome c protein levels. Cardiomyocyte loss due to oxidative stress-mediated apoptosis is a key event in DOX-induced cytotoxicity. DIA had protective effects on DOX-induced cardiotoxicity, via mitoK ATP integrity, especially with elevated SUR2A levels; but also by a cascade including SOD/AMPK/ERK1/2. Therefore, DIA may be considered a candidate agent for protecting cardiomyocytes against DOX chemotherapy. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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