Research Paper Advance Articles

Dexrazoxane ameliorates radiation-induced heart disease in a rat model

Dexrazoxane decreases functional damage and structural injury in the rat heart after irradiation. (A) Representative M-mode echocardiograms for each group. (B, C) Representative HE and Masson staining (×200, scale bar =100 μm) of hearts from each group (n=7-11, respectively). (D) Subcellular abnormalities in mitochondria, sarcomeres, and myofilaments identified by TEM (×10K). (E) Kaplan-Meier analysis of rat survival in each group. Exposure to whole heart irradiation significantly reduced overall survival time (CON vs RT, p =0.029). A non-significant trend for a long-term survival benefit of DZR was observed. (F) Irradiation significantly decreased EF in rats within 8 weeks. No significant differences were observed among the groups (n=3 at every time point for each group) after 8 weeks. (G) H9C2 cells were pre-treated with or without DZR (100, 200, and 400 μM) before a single 10 Gy X-ray irradiation. 24 h after irradiation, radiation-induced apoptosis-related injuries were reduced in cardiomyocytes pre-treated with 200 and 400 μM DZR. (H) Serum levels of cardiac troponin I (cTnI) were assessed at week 24 after irradiation. cTnI levels in CON and DZR groups were 30.13 ± 7.94 and 36.58 ± 8.97 pg/mL (n=5), respectively. Irradiation significantly increased cTnI levels in irradiated rats. cTnI levels were as follows: 147.00 ± 2.46 pg/mL in RT group (vs CON, pppp p

Figure 1. Dexrazoxane decreases functional damage and structural injury in the rat heart after irradiation. (A) Representative M-mode echocardiograms for each group. (B, C) Representative HE and Masson staining (×200, scale bar =100 μm) of hearts from each group (n=7-11, respectively). (D) Subcellular abnormalities in mitochondria, sarcomeres, and myofilaments identified by TEM (×10K). (E) Kaplan-Meier analysis of rat survival in each group. Exposure to whole heart irradiation significantly reduced overall survival time (CON vs RT, p =0.029). A non-significant trend for a long-term survival benefit of DZR was observed. (F) Irradiation significantly decreased EF in rats within 8 weeks. No significant differences were observed among the groups (n=3 at every time point for each group) after 8 weeks. (G) H9C2 cells were pre-treated with or without DZR (100, 200, and 400 μM) before a single 10 Gy X-ray irradiation. 24 h after irradiation, radiation-induced apoptosis-related injuries were reduced in cardiomyocytes pre-treated with 200 and 400 μM DZR. (H) Serum levels of cardiac troponin I (cTnI) were assessed at week 24 after irradiation. cTnI levels in CON and DZR groups were 30.13 ± 7.94 and 36.58 ± 8.97 pg/mL (n=5), respectively. Irradiation significantly increased cTnI levels in irradiated rats. cTnI levels were as follows: 147.00 ± 2.46 pg/mL in RT group (vs CON, p<0.01, n=8), 78.95 ± 12.81 pg/mL in RT+ H-DZR group (vs RT, p<0.01, n=11), 110.80 ± 11.36 pg/mL in RT +L-DZR group (vs RT, p<0.05, n=9). Data are expressed as mean ± SEM, *: p <0.05, **: p <0.01.