Open Access

Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats

  • Authors:
    • Rong Wu
    • Ping‑An Yao
    • Hui‑Lin Wang
    • Yan Gao
    • Hai‑Lun Yu
    • Lei Wang
    • Xiao‑Hua Cui
    • Xu Xu
    • Jian‑Ping Gao
  • View Affiliations

  • Published online on: July 24, 2018     https://doi.org/10.3892/mmr.2018.9310
  • Pages: 3229-3241
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cordyceps sinensis (CS) is a prominent medicinal herb in traditional Chinese medicine, and fermented CS is frequently used as a substitute for natural CS. Doxorubicin (DOX), an antitumor drug used in chemotherapy, is limited by its poor cardiotoxicity. The aim of the present study was to evaluate the protective effect of fermented CS against DOX‑induced cardiotoxicity and the potential underlying mechanisms. Male Sprague‑Dawley rats (180‑200 g) were randomly assigned to seven different treatment groups: Normal control, DOX control, DOX+captopril (0.05 g/kg), 0.75, 1.5 and 3 g/kg DOX+CS, and the CS (1.5 g/kg) control. Histopathological changes, cardiac energy metabolism, cyclic adenosine monophosphate (cAMP) signaling and the associated mRNA expression of AMP‑activated protein kinase (AMPK) were then evaluated. Fermented CS decreased the left ventricular weight index, heart weight index and mortality; however, it increased diastolic blood pressure and mean arterial pressure. In addition, it shortened the duration of the QRS complex and Sα‑T segment, decreased serum creatine kinase (CK) and aspartate aminotransferase activity, inhibited histopathological changes and reduced brain natriuretic peptide content. Treatment with fermented CS also increased the activities of superoxide dismutase and glutathione peroxidase, reduced malondialdehyde content, increased the mitochondrial activities of Na+K+‑adenosine 5'‑triphosphate (ATP) ase, Ca2+Mg2+‑ATPase and CK, and increased the creatine phosphate/ATP ratio and AMP/ATP ratio. Furthermore, it decreased the ATP/adenosine 5'‑diphosphate (ADP) ratio, upregulated AMPKα2 expression, reduced the activity of serum phosphodiesterases (PDEs) and increased myocardial cAMP content. The results of the present study demonstrated that fermented CS attenuated DOX‑induced cardiotoxicity by inhibiting myocardial hypertrophy and myocardial damage, ameliorating systolic function and the antioxidant enzyme system, improving cardiac energy metabolism, depressing the activities of PDEs, and by upregulating the cAMP and AMPK signaling pathways. Thus, fermented CS may be a candidate for the prevention of DOX‑induced cardiotoxicity, cardiac energy impairment and against a number of cardiac diseases.
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September-2018
Volume 18 Issue 3

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Spandidos Publications style
Wu R, Yao PA, Wang HL, Gao Y, Yu HL, Wang L, Cui XH, Xu X and Gao JP: Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats. Mol Med Rep 18: 3229-3241, 2018.
APA
Wu, R., Yao, P., Wang, H., Gao, Y., Yu, H., Wang, L. ... Gao, J. (2018). Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats. Molecular Medicine Reports, 18, 3229-3241. https://doi.org/10.3892/mmr.2018.9310
MLA
Wu, R., Yao, P., Wang, H., Gao, Y., Yu, H., Wang, L., Cui, X., Xu, X., Gao, J."Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats". Molecular Medicine Reports 18.3 (2018): 3229-3241.
Chicago
Wu, R., Yao, P., Wang, H., Gao, Y., Yu, H., Wang, L., Cui, X., Xu, X., Gao, J."Effect of fermented Cordyceps sinensis on doxorubicin‑induced cardiotoxicity in rats". Molecular Medicine Reports 18, no. 3 (2018): 3229-3241. https://doi.org/10.3892/mmr.2018.9310