Key result
Combined 3-BrPA and TMZ worsens rat heart function vs either agent alone, increasing myocardial apoptosis.
Why the study?
Because TMZ and 3-BrPA separately inhibit fatty acid and glucose metabolism, the two main cardiac energy sources, investigating their combined effects on the heart was necessary.
Does the combined use of Trimetazidine and 3-Bromopyruvate cause cardiotoxicity in male Wistar rats?
RCT (n=40)
Randomized
Does the combined use of Trimetazidine and 3-Bromopyruvate cause cardiotoxicity in male Wistar rats?
The concurrent use of 3-bromopyruvate and trimetazidine induces cardiotoxicity in a rat model by simultaneously inhibiting glucose and fatty acid metabolism, suggesting these agents should not be used together.
Answers are grounded in this paper and cite their sources.
May worsen cardiac function when combined in rats; hypothesis-generating and should not yet inform clinical practice.
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 tumor therapy. Because TMZ and 3-BrPA can separately inhibit the 2 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 4 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 adenosine triphosphate, oxidative stress-related factors (ROS, glutathione, oxidized glutathione, malondialdehyde, superoxide dismutase and total antioxidant capacity), 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 adenosine triphosphate levels, and increased oxidative stress and myocardial apoptosis. In conclusion, 3-BrPA and TMZ are not recommended for concurrent use.
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A 2021 study conducted an RCT in Cardiotoxicity (n=40). 3-Bromopyruvate (3-BrPA) combined with Trimetazidine (TMZ) vs. Control group, TMZ alone, and 3-BrPA alone was evaluated on Heart function, ATP levels, oxidative stress, and apoptosis. The combination of 3-BrPA and TMZ worsened heart function, decreased ATP levels, and increased oxidative stress and myocardial apoptosis in rats compared to either agent alone or control.
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