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Updated: Oct 4, 2025
A Doxorubicin-induced Cardiomyopathy Model in Adult Zebrafish
Published on: June 7, 2018
Protective effects of necrostatin-1 on doxorubicin-induced cardiotoxicity in rat heart
Zeynep Erdogmus Ozgen1, Meral Erdinc2, İlker Kelle2
1Department of Pharmacology, School of Pharmacy, 37507Dicle University, Diyarbakir, Turkey.
Abstract:
Background: Doxorubicin (Dox) is one of the most effective antineoplastic drugs which has severe cardiotoxic effects, limiting its clinical usage. Though the exact mechanism of doxorubicin-induced cardiotoxicity is yet to be elucidated, it is shown that production of reactive oxygen species (ROS) increases oxidative stress and leads to cardiomyocyte apoptosis and necroptosis which is also defined as a programmed cell death.Purpose: In the present study, we investigate the effects of necrostatin-1 (Nec-1)-an inhibitor of receptor interaction proteins 1 (RIP1) and necroptosis-on doxorubicin-induced cardiotoxicity in rats.Research Design: Hearts were isolated and perfused by the Langendorff system in all four groups. Perfusion pressure (PP), left ventricular developed pressure (LVDP) and heart rate per minute (HR), LV (dP/dt) max, and LV (dP/dt) min which shows cardiac contractility and relaxation were recorded.Results: Results showed that PP significantly increased with Dox treatment and significantly decreased with Nec-1 treatment, while HR, LVDP, LV (dP/dt) max, and LV (dP/dt) min values significantly decreased with the Dox-treated group and significantly increased with Nec-1 treatment. Also with Nec-1 treatment, gene expression levels of anti-apoptotic Bcl-2 significantly increased and pro-apoptotic protein Bax, apoptotic marker caspase-3, and Nox-2 significantly decreased compared to the Dox-treated group. In heart tissues, MDA levels were significantly increased with Dox and decreased with Nec-1 treatment. These results were supported by the histological analysis indicated that Nec-1 reduced doxorubicin-induced cellular injury.Conclusions: In conclusion, our data indicate that Nec-1 ameliorates doxorubicin-induced cardiotoxicity by reducing oxidative stress injury and attenuating apoptosis and necroptosis.
Insights
Necrostatin-1 (Nec-1) treatment reduced doxorubicin-induced cardiotoxicity in rats by decreasing oxidative stress and programmed cell death. This suggests Nec-1 may protect against chemotherapy-related heart damage.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Doxorubicin (Dox) is a potent anticancer drug with significant cardiotoxicity, limiting its use.
- Doxorubicin-induced cardiotoxicity involves oxidative stress, apoptosis, and necroptosis (programmed cell death).
Purpose of the Study:
- To investigate the protective effects of necrostatin-1 (Nec-1) against doxorubicin-induced cardiotoxicity in a rat model.
- To assess Nec-1's impact on cardiac function, oxidative stress markers, and cell death pathways.
Main Methods:
- Isolated rat hearts were perfused using the Langendorff system.
- Cardiac function parameters (pressure, heart rate, contractility) were measured.
- Gene expression of apoptosis-related proteins (Bcl-2, Bax, caspase-3, Nox-2) and malondialdehyde (MDA) levels were analyzed.
Main Results:
- Doxorubicin treatment worsened cardiac function and increased oxidative stress (MDA levels).
- Nec-1 treatment significantly improved cardiac function and reduced MDA levels compared to doxorubicin alone.
- Nec-1 upregulated anti-apoptotic Bcl-2 and downregulated pro-apoptotic Bax, caspase-3, and Nox-2, indicating reduced apoptosis and necroptosis.
Conclusions:
- Necrostatin-1 effectively ameliorates doxorubicin-induced cardiotoxicity in rats.
- Nec-1 protects the heart by reducing oxidative stress and inhibiting apoptosis and necroptosis.
- Nec-1 shows potential as a therapeutic agent to mitigate chemotherapy-induced heart damage.
