Oxidative stress biomarkers and myocardial dysfunction in a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy

Background

Chemotherapy, although improving survival rates in breast cancer patients, is associated with heightened risks of myocardial dysfunction and heart failure. This study explores the association of oxidative stress biomarkers with myocardial dysfunction in a rat model induced by doxorubicin and trastuzumab.

Methods

Forty-two rats were allocated into groups receiving various treatments including control, doxorubicin only, and doxorubicin plus trastuzumab. Doxorubicin and trastuzumab were sequentially administered over 28 days at 2-week intervals. Echocardiography with speckle-tracking was utilized to measure left ventricular end-systolic dimension and longitudinal strain (LS). Blood samples were collected from the inferior vena cava before sacrifice for biomarker analysis, focusing on oxidative stress indicators including superoxide dismutase (SOD) and glutathione (GSH). Myocardium fibrosis area was measured using Masson's trichrome staining.

Results

The combination of doxorubicin and trastuzumab significantly increased the LV end-systolic dimension and worsened LS compared to the control group (all P < .05). Levels of oxidative stress biomarkers, including SOD and glutathione, were significantly deteriorated in the chemotherapy groups. Oxidative stress biomarkers demonstrated a strong correlation with measures of myocardial dysfunction. SOD showed a correlation coefficient of 0.609 with LS (P = 0.0056). Glutathione (GSH) showed a correlation coefficient of -0.477 with LS (P = 0.0388). Additionally, LS was well correlated with fibrosis area, showing a correlation coefficient of -0.487 (P = 0.0347).

Conclusions

In a doxorubicin- and trastuzumab-induced rat model of cardiomyopathy, oxidative stress biomarkers were correlated with myocardial dysfunction, as represented by LS. The findings suggest that monitoring these biomarkers could enhance early detection and prevention strategies for chemotherapy-induced cardiomyopathy.

A representative image of strain

Correlation between parameters