Cytoprotective potential of anti-ischemic drugs against chemotherapy-induced cardiotoxicity in H9c2 myoblast cell line

To investigate potential prevention or attenuation of anti- cancer drug induced cardiotoxicity using anti-ischemic drugs, a rat myoblast (H9c2) cell line was used as our in vitro cardiac model. Irinotecan and doxorubicin were found to be cytotoxic for the H9c2 cell line with IC₅₀ of 30.69 ± 6.20 and 20.94 ± 6.05 mmol L^-1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC₅₀ could not be calculated. When 100 mmol L^-1 doxorubicin was incubated for 72 hours with 50 mmol L^-1 diltiazem, 100 mmol L^-1 dexrazoxane and 100 mmol L^-1 losartan, respectively, there was a 58.7 ± 10.2, 52.2 ± 11.7 and 44.7 ± 5.4 % reduction in cell death. When 200 mmol L^-1 irinotecan was incubated for 72 hours with 100 mmol L^-1 dexrazoxane, losartan and diltiazem, respectively, a 27.7 ± 6.9, 25.6 ± 5.1, and 19.1 ± 2.3 % reduction in cell death was observed. Our data suggests that losartan and diltiazem were as effective as dexrazoxane in protecting the cells against irinotecan- and doxorubicin-induced cell toxicity. These findings offer potential uses of anti- -ischemic drugs for ablation of cytotoxicity in response to mitochondrial injury, thereby improving patient outcomes and reducing health-care costs.