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

Abstract

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.

Modulation of doxorubicin-induced expression of the multidrug resistance gene in breast cancer cells by diltiazem and protection against cardiotoxicity in experimental animals

“…Our data are also in a consistent with Feridooni et al who found potential prevention or attenuation of anti-cancer drug-induced cardiotoxicity (Irinotecan and DOX) by using anti-ischemic drugs (losartan and DIL) plus dexrazoxane in (H9c2) rat cardiomyoblast cell line. They found that losartan and DIL were as effective as dexrazoxane in protecting the cardiac cells against irinotecan- and DOX-induced toxicity [32].…”

Investigation of the Antiremodeling Effects of Losartan, Mirabegron and Their Combination on the Development of Doxorubicin-Induced Chronic Cardiotoxicity in a Rat Model

“…Among the inhibitors of RAAS overactivation, angiotensin-II receptor blockers (ARBs) are widely used drugs to prevent the progression of chronic heart failure in various comorbidities [17,18]. ARB losartan showed cardioprotective effects against experimental DOXO-induced cardiotoxicity [19,20]. Indeed, based on the results of clinical trials, inhibition of RAAS overactivation with ARBs has also shown beneficial effects on the development of DOXO-induced chronic cardiotoxicity [13].…”