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Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats

  • Authors:
    • Meng‑Lin Liu
    • Meng‑Long Wang
    • Jing‑Jun Lv
    • Jie Wei
    • Jun Wan
  • View Affiliations / Copyright

    Affiliations: Department of Emergency, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Wuhan University, Hubei Key Laboratory of Cardiology, Wuhan, Hubei 430060, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3425-3431
    |
    Published online on: February 13, 2018
       https://doi.org/10.3892/etm.2018.5862
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Abstract

Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP‑dependent potassium (K‑ATP) channels, blocks the cardioprotective effects of mitochondrial K‑ATP channel openers and induces apoptosis in rodent pancreatic islet β‑cell lines. However, little is known about the role of Gli in ADR‑induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR‑induced cardiotoxicity in rats. A total of 60 male Sprague‑Dawley rats were divided into the following 4 groups: i) Control; ii) Gli; iii) ADR; and iv) Gli+ADR (n=15 in each). The rats in the ADR and Gli+ADR groups were treated with ADR (intraperitoneal, 2.5 mg/kg/week) for 6 weeks. The rats in the Gli and Gli+ADR groups received Gli at a dose of 12 mg/kg/day via gastric lavage for 30 days from the eighth week of the study. Following the completion of Gli treatment, cardiac function was assessed by echocardiography, and the rats were sacrificed. The hearts were subsequently harvested for analysis. The rats in the ADR group demonstrated significantly impaired cardiac function and increased levels of oxidative stress, endoplasmic reticulum stress (ERS) and apoptosis in the heart compared with rats in the control and Gli groups (without ADR treatment). These abnormalities were exacerbated by Gli in the Gli+ADR group. Gli treatment decreased cardiac function and significantly increased oxidative stress, ERS and apoptosis levels in myocardial tissues in rats treated with ADR. The findings indicated that Gli triggers oxidative stress‑induced ERS, and thus exacerbates ADR‑induced cardiotoxicity in rats.
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Copy and paste a formatted citation
Spandidos Publications style
Liu ML, Wang ML, Lv JJ, Wei J and Wan J: Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats. Exp Ther Med 15: 3425-3431, 2018.
APA
Liu, M., Wang, M., Lv, J., Wei, J., & Wan, J. (2018). Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats. Experimental and Therapeutic Medicine, 15, 3425-3431. https://doi.org/10.3892/etm.2018.5862
MLA
Liu, M., Wang, M., Lv, J., Wei, J., Wan, J."Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats". Experimental and Therapeutic Medicine 15.4 (2018): 3425-3431.
Chicago
Liu, M., Wang, M., Lv, J., Wei, J., Wan, J."Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3425-3431. https://doi.org/10.3892/etm.2018.5862
Copy and paste a formatted citation
x
Spandidos Publications style
Liu ML, Wang ML, Lv JJ, Wei J and Wan J: Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats. Exp Ther Med 15: 3425-3431, 2018.
APA
Liu, M., Wang, M., Lv, J., Wei, J., & Wan, J. (2018). Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats. Experimental and Therapeutic Medicine, 15, 3425-3431. https://doi.org/10.3892/etm.2018.5862
MLA
Liu, M., Wang, M., Lv, J., Wei, J., Wan, J."Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats". Experimental and Therapeutic Medicine 15.4 (2018): 3425-3431.
Chicago
Liu, M., Wang, M., Lv, J., Wei, J., Wan, J."Glibenclamide exacerbates adriamycin-induced cardiotoxicity by activating oxidative stress-induced endoplasmic reticulum stress in rats". Experimental and Therapeutic Medicine 15, no. 4 (2018): 3425-3431. https://doi.org/10.3892/etm.2018.5862
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