Acta Pharm. 63 (2013) 493-503

 

full paper

Original research paper

 

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

TIAM FERIDOONI, CHRIS MAC DONALD, DI SHAO, POLLEN YEUNG and REMIGIUS U. AGU

Remigius.agu@dal.ca

1 Department of Pharmacology, Dalhousie University Halifax, Nova Scotia, Canada B3H 4R2, Canada

2 Biopharmaceutics and Drug Delivery Laboratory, Dalhousie University, Halifax, NS B3H 3J5, Canada

3 Pharmacokinetics and Metabolism Laboratory, College of Pharmacy Dalhousie University, Halifax NS B3H 3J5, Canada

Accepted September 30, 2013

 

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 L1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC50 could not be calculated. When 100 mmol L1 doxorubicin was incubated for 72 hours with 50 mmol L1 diltiazem, 100 mmol L1 dexrazoxane and 100 μmol L1 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 L1 irinotecan was incubated for 72 hours with 100 mmol L1 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.

 

Keywords: rat myoblast (H9C2), cytoprotection, dexrazoxane, doxorubicin, diltiazem, irinotecan