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Combined usage of trimetazidine with 3-bromopyruvate may lead to cardiotoxicity by activating oxidative stress and apoptosis in rats.
Journal of Cardiovascular Pharmacology  (IF3.105),  Pub Date : 2021-09-06, DOI: 10.1097/fjc.0000000000001136
Min Zheng, Chengchuang Zhan, Nan Bai, Juncai Bai, Chaoqun Nie, Jing Chi, Xue Ding, Jiaren Liu, Wei Yang

The energy used by the heart is generated mainly by the metabolism of fatty acids and glucose. Trimetazidine (TMZ) inhibits fatty acid metabolism and is used for the treatment of heart diseases such as heart failure. 3-Bromopyruvate (3-BrPA) can suppress glucose metabolism, and it is considered a promising candidate agent for tumour therapy. As TMZ and 3-BrPA can separately inhibit the two main cardiac energy sources, it is necessary to investigate the effects of 3-BrPA combined with TMZ on the heart.Forty male Wistar rats were randomly divided into four groups: a control group, a TMZ group, a 3-BrPA group, and a 3-BrPA+TMZ group. Weight was recorded every day, and echocardiography was performed 14 days later. Heart function, the levels of ATP, oxidative stress-related factors (ROS, GSH, GSSG, MDA, SOD, and TAC) and apoptosis in heart tissues were assessed to evaluate the effects of 3-BrPA and TMZ on the heart. In our study, no obvious changes occurred in the 3-BrPA group or the TMZ group compared with the control group. The combination of 3-BrPA and TMZ worsened heart function, decreased ATP levels and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.