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.
Keywords: canagliflozin; cardiomyocyte injury; cardiotoxicity; pirarubicin.