Canagliflozin is a potential cardioprotective drug but exerts no significant effects on pirarubicin‑induced cardiotoxicity in rats

Shi,Hongwei; Zeng,Qingfu; Wei,Yunjie; Yang,Hong; Tang,Heng; Wang,Dan; Pu,Peng; Feng,Rui

doi:10.3892/mmr.2021.12342

Canagliflozin is a potential cardioprotective drug but exerts no significant effects on pirarubicin‑induced cardiotoxicity in rats

Authors:
- Hongwei Shi
- Qingfu Zeng
- Yunjie Wei
- Hong Yang
- Heng Tang
- Dan Wang
- Peng Pu
- Rui Feng
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Affiliations: Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430079, P.R. China, Department of Vascular Surgery, The Second Affiliated Hospital of Nanchang University, Donghu, Nanchang, Jiangxi 330006, P.R. China, Department of Cardiology, Hubei Shiyan Taihe Hospital, Wuhan, Hubei 430000, P.R. China, Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Yuanjiagang, Yuzhong, Chongqing 400042, P.R. China, Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, Yuanjiagang, Yuzhong, Chongqing 400042, P.R. China, Department of Cardiology, Chongqing Red Cross Hospital, Yuzhong, Chongqing 400020, P.R. China
Published online on: August 5, 2021 https://doi.org/10.3892/mmr.2021.12342
Article Number: 703

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Abstract

Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various types of cancer, but its cardiotoxicity cannot be ignored. Canagliflozin, the first sodium‑glucose co‑transporter‑2 inhibitor approved by the USA FDA, has been shown to have a significant effect on cardiovascular damage caused by diabetes. However, it has not been reported whether it can resist THP‑induced cardiotoxicity. The aim of the present study was to investigate the effect of canagliflozin on THP‑induced cardiotoxicity and its mechanism. A rat model of cardiotoxicity induced by THP was established and canagliflozin treatment was performed at the same time. The changes of electrocardiography, cardiac coefficient and echocardiogram were observed. The levels of lactate dehydrogenase, brain natriuretic peptide, creatine kinase MB, cardiac troponin T, superoxide dismutase (SOD) and malondialdehyde were detected. The expression of SOD2, NADPH oxidase 2, pro/cleaved‑caspase‑ and Bcl‑2/Bax were evaluated by western blotting. The primary culture of cardiomyocytes was prepared to explore the effect in vitro. After eight weeks, a series of cardiotoxicity manifestations were observed in THP rats. However, canagliflozin treatment had no significant effect on the above adverse reactions. Similarly, further studies showed that canagliflozin had no significant effect on THP‑induced cardiomyocyte injury in vitro. The present study showed that there was no significant protective effect of canagliflozin on THP‑induced cardiotoxicity and cardiomyocyte injury.

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