Cardioprotective action of the aqueous extract of Terminalia arjuna bark against toxicity induced by doxorubicin.

Background: The aqueous extract of Terminalia arjuna (TA) bark (TA) has been shown to have a direct inotropic effect on ventricular myocytes. Active constituents of TA contain various flavonoids and proanthocyanidins, some of which are known to have antioxidant activities. Whether TA affords a cardioprotective action against oxidative stress (OS) remains unclear.

Purpose: Increased OS is one of the major mechanisms underlying cardiotoxicity induced by doxorubicin (DOX), a commonly-used anticancer agent. The aim of the present study was to investigate potential cardioprotective effect of TA against DOX-induced OS and cardiac dysfunction.

Methods: OS and cytotoxicity were induced by 1 µM DOX for 24 h in H9c2 cells, a cardiac tissue-derived cell line, and left ventricular (LV) dysfunction was induced by intrapleural injection of DOX (accumulative 20 mg/kg body weight) to mice. Cellular oxidative levels and morphology were assessed using microscopy and oxidative-sensitive fluorescent dyes with and without co-treatment with TA. LV function was monitored weekly with echocardiography.

Results: TA reduced OS and preserved mitochondria and cell growth of H9c2 cells against DOX treatment. TA (in drinking water) attenuated the decreased LV function and altered myocardial structure caused by DOX treatment.

Conclusion: TA exerts a protective action against cardiotoxicity caused by DOX in part via suppression of OS. Thus, TA is a promising cardiotonic in adjuvant cancer chemotherapy.