Open Access

Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats

  • Authors:
    • Zhifeng Zhao
    • Jinghan Li
    • Bin Zheng
    • Yingran Liang
    • Jing Shi
    • Jianping Zhang
    • Xue Han
    • Li Chu
    • Xi Chu
    • Yonggang Gao
  • View Affiliations

  • Published online on: October 14, 2020     https://doi.org/10.3892/mmr.2020.11587
  • Pages: 5271-5281
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Arsenic trioxide (ATO) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (CRT), the critical ingredient of saffron. Sprague‑Dawley rats were then randomly divided into four groups (n=10/group): i) Control group; ii) ATO group, iii) CRT‑low (20 mg/kg) group; and iv) CRT‑high (40 mg/kg) group. Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and CRT groups were administered with either 20 and 40 mg/kg CRT. Following 6 h, all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days. Cardiotoxicity was indicated by changes in electrocardiographic (ECG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis‑related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. Cardiotoxicity was induced in male Sprague‑Dawley rats with ATO (5 mg/kg). CRT (20 and 40 mg/kg) and ATO were co‑administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J‑point elevation induced by ATO in rats. Histological changes were evaluated via hematoxylin and eosin staining. CRT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione‑peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, CRT downregulated the expression levels of the pro‑inflammatory factors IL‑1, TNF‑α, IL‑6, Bax and p65, as well as increased the expression of Bcl‑2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that CRT treatment effectively ameliorated ATO‑induced cardiotoxicity. The protective effects of CRT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment, and additional clinical applications are possible, but warrant further investigation.
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December-2020
Volume 22 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Zhao Z, Li J, Zheng B, Liang Y, Shi J, Zhang J, Han X, Chu L, Chu X, Gao Y, Gao Y, et al: Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats. Mol Med Rep 22: 5271-5281, 2020
APA
Zhao, Z., Li, J., Zheng, B., Liang, Y., Shi, J., Zhang, J. ... Gao, Y. (2020). Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats. Molecular Medicine Reports, 22, 5271-5281. https://doi.org/10.3892/mmr.2020.11587
MLA
Zhao, Z., Li, J., Zheng, B., Liang, Y., Shi, J., Zhang, J., Han, X., Chu, L., Chu, X., Gao, Y."Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats". Molecular Medicine Reports 22.6 (2020): 5271-5281.
Chicago
Zhao, Z., Li, J., Zheng, B., Liang, Y., Shi, J., Zhang, J., Han, X., Chu, L., Chu, X., Gao, Y."Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity in rats". Molecular Medicine Reports 22, no. 6 (2020): 5271-5281. https://doi.org/10.3892/mmr.2020.11587