Tirzepatide Protects the Heart from Doxorubicin-induced Cardiotoxicity via Modulating ER Stress
DOI:
https://doi.org/10.7492/ma41ae60Abstract
Background
Doxorubicin is an effective chemotherapy treatment that has the greatest drawback of dose dependant cardiotoxicity that is largely due to oxidative stress, mitochondrial dysfunctional response and excessive endoplasmic reticulum (ER) stress. Recently Tirzepatide, a dual GIP/GLP-1 agonist receptor has proven to have cardiometabolic activity, but its cardiac injury protection during chemotherapy remains unexplained.
Objective
To investigate the impact of tirzepatide on mitigation of doxorubicin-induced cardiotoxicity and to determine the impact of tirzepatide on the regulation of the ER stress-related pathways of cardiac tissue.
Methods
They made experiments on both in vivo rodent models and in vitro cardiomyocyte in, as cardiac functioning, histopathology, apoptosis markers and ER stress proteins were assessed after exposure of doxorubicin. Cardiac injury was measured by treating Tirzepatide to animals beforehand or in combination with it echocardiography, serum biomarkers, and molecular measurement of the ER stress pathway (ERPK-eIF2 -ATF4 and AUTOF). The level of oxidative stress and mitochondrial integrity was also assessed.
Results
Tirzepatide significantly enhanced the left ventricular performance and reduced the concentrations of serum cardiac injury in models that were treated with doxorubicin. Histology indicated that there was a high inhibited cardiomyocyte-apoptosis and fibrosis. Tirzepatide suppressed ER stress mechanism in a key down-regulation of the PERK/eIF2 signaling/CHIP and mitochondrial recovery of the membrane potential and mitochondrial reduction of the ROS. These recorded protective effects with in vitro dose-dependency on cardiomyocytes.
Conclusion
Tirzepatide may prove useful in preventing doxorubicin-induced cardiotoxicity; in this case, it inhibits ER stress pathways and reduces the impact of oxidative and mitochondrial injury. These findings recommend it as a supplement of heart protective therapy in patients undergoing anthracycline chemotherapy.
