Oxidative Stress Biomarkers Predict Myocardial Dysfunction in a Chemotherapy-Induced Rat Model

Objectives: Chemotherapy improves survival in breast cancer patients but increases the risk of myocardial dysfunction and heart failure. Since early prediction of cardiomyopathy remains difficult, biomarkers are needed for detecting myocardial damage before heart failure develops. This study examines the association between oxidative stress biomarkers and myocardial dysfunction in a chemotherapy-induced rat model. Methods: Forty-two rats were randomized into four groups: control (n = 7), doxorubicin only (n = 7), doxorubicin plus trastuzumab (n = 7), and doxorubicin plus trastuzumab with cardioprotective intervention (n = 21). Doxorubicin and trastuzumab were administered sequentially over 28 days. Echocardiography with speckle-tracking was utilized to measure longitudinal strain (LS, -%). Reduced LS was defined by a LS with a median value less than 23% on day 28. Blood samples were collected for biomarker analysis, focusing on superoxide dismutase (SOD) and glutathione (GSH). Myocardium fibrosis was assessed using Masson's trichrome staining. Results: Thirty-four rats survived and underwent LS analysis. All rats treated with doxorubicin and trastuzumab exhibited reduced LS, while those receiving cardioprotective intervention maintained preserved LS on day 28. The reduced LS group had significantly lower SOD and higher GSH levels compared to the preserved LS group. SOD and GSH correlated strongly with LS (SOD, r = 0.590, p = 0.001; GSH, r = -0.590, p = 0.003), and LS correlated with fibrosis area (r = -0.660, p < 0.001). SOD and GSH effectively predicted reduced LS. Conclusions: In a rat model of chemotherapy-induced cardiomyopathy, oxidative stress biomarkers correlated with myocardial dysfunction, as indicated by LS. These findings highlight the potential of biomarker monitoring to improve early detection and prevention strategies for chemotherapy-induced cardiomyopathy.