Key result
Diminazene protects against tebuconazole-induced cardiotoxicity and dysfunction in preclinical models.
Why the study?
Tebuconazole exposure is increasingly linked to adverse cardiovascular outcomes, but no specific therapeutic approaches exist to counteract its cardiotoxicity.
Does Diminazene protect against Tebuconazole-induced cardiotoxicity in cardiomyoblast and isolated rat heart models?
Does Diminazene protect against Tebuconazole-induced cardiotoxicity in cardiomyoblast and isolated rat heart models?
Diminazene demonstrates promising cardioprotective effects against tebuconazole-induced cardiotoxicity in experimental models by mitigating oxidative stress, electrophysiological dysfunction, and ACE2 downregulation.
DIZE may attenuate TEB-induced cardiotoxicity in preclinical models; leaves open whether it offers a viable strategy for human environmental exposure.
Background/Objectives: Tebuconazole (TEB) is a fungicide whose exposure has been increasingly linked to adverse cardiovascular outcomes. However, no specific therapeutic approaches are available to counteract TEB-induced cardiotoxicity, underscoring the need for new pharmacological strategies. Diminazene (DIZE) has emerged as a promising cardioprotective agent through its modulatory effects on the renin-angiotensin system (RAS), particularly via activation of the ACE2/Ang-(1–7)/Mas receptor. Methods: This study investigated whether DIZE protects against TEB cardiotoxicity using an in vitro model utilizing H9c2 cardiomyoblasts and an ex vivo model employing Langendorff-perfused rat hearts. Results: In cardiomyoblasts, TEB induced a dose-dependent reduction in cell viability, accompanied by increased apoptotic/necrotic cell death. A concentration of 100 µM TEB, representing an intermediate toxicity profile, was selected for subsequent experiments. Co-exposure to DIZE (100–1000 µM) attenuated TEB-induced cytotoxicity in a concentration-dependent manner, restored cell viability and reduced oxidative and nitrosative stress markers, specifically reactive oxygen species (measured via DHE) and nitric oxide (via DAF-2 DA). Furthermore, TEB showed lower mean ACE2 expression and DIZE prevented the downregulation. In isolated heart preparations, TEB caused pronounced mechanical and electrophysiological dysfunction. Mechanically, TEB reduced left ventricular developed pressure, impaired contractility, increased end-diastolic pressure, and prolonged systolic duration. Electrophysiologically, TEB induced bradycardia, PR prolongation, and QT/QTc and T-wave prolongation, indicating delayed atrioventricular conduction and ventricular repolarization. DIZE markedly attenuated both the mechanical and electrical abnormalities induced by TEB. Conclusions: These findings provide the first experimental evidence of DIZE against TEB-induced cardiac injury and support further investigation of its potential against pesticide-induced cardiotoxicity.
No takes yet. Share an insight, caveat, or question.
Resende et al. (2026) studied Tebuconazole-induced cardiotoxicity. Diminazene vs. Tebuconazole alone was evaluated on Cell viability, mechanical dysfunction, and electrophysiological dysfunction. Diminazene (100–1000 µM) attenuated tebuconazole-induced cytotoxicity, oxidative stress, and mechanical and electrophysiological dysfunction in cardiomyoblasts and isolated rat hearts.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: