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Original scientific paper

https://doi.org/10.2478/acph-2013-0038

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

FERIDOONI
TIAM FERIDOONI ; Department of Pharmacology, Dalhousie University Halifax, Nova Scotia, Canada B3H 4R2, Canada
CHRIS MAC DONALD ; Biopharmaceutics and Drug Delivery Laboratory, Dalhousie University, Halifax, NS B3H 3J5, Canada
DI SHAO ; Department of Pharmacology, Dalhousie University Halifax, Nova Scotia, Canada B3H 4R2, Canada
POLLEN YEUNG ; Pharmacokinetics and Metabolism Laboratory, College of Pharmacy Dalhousie University, Halifax NS B3H 3J5, Canada
REMIGIUS U. AGU orcid id orcid.org/0000-0001-6091-1840 ; Department of Pharmacology, Dalhousie University Halifax, Nova Scotia, Canada B3H 4R2, Canada


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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 mol L–1, respectively. 5-Flurouracil and cladribine were not cytotoxic and thus IC50 could not be calculated. When 100 mol L–1 doxorubicin was incubated for 72 hours with 50 mol L–1 diltiazem, 100 mol L–1 dexrazoxane and 100 μmol 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 mol L–1 irinotecan was incubated for 72 hours with 100 mol 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.

Keywords

rat myoblast (H9C2); cytoprotection; dexrazoxane; doxorubicin; diltiazem; irinotecan

Hrčak ID:

110457

URI

https://hrcak.srce.hr/110457

Publication date:

31.12.2013.

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