Arsenic Trioxide Toxicity in H9c2 Myoblasts—Damage to Cell Organelles and Possible Amelioration with Boerhavia diffusa V. P. Vineetha • A. Prathapan • R. S. Soumya • K. G. Raghu Ó Springer Science+Business Media New York 2012 Abstract Arsenic trioxide (ATO) has been long used as a chemotherapeutic agent because of its significant anticancer property. Unfortunately, the use of ATO is limited due to its cardiotoxic effects. The present study evaluates the pro- tective property of ethanolic extract of Boerhavia diffusa (BDE) against ATO-induced toxicity on various cell organelles in H9c2 cardiomyocytes. The effects of different concentrations of ATO (5, 7.5 and 10 lM) on cell organ- elles like mitochondria, endoplasmic reticulum (ER), lysosome and actin, generation of reactive oxygen species, antioxidant enzyme status and intracellular calcium over- load were evaluated. ATO significantly (P B 0.05) altered mitochondrial transmembrane potential, intracellular cal- cium level, ER, lysosomal activity and F-actin network in addition to induction of oxidative stress. Co-treatment with BDE protected the cardiomyocytes from the adverse effects of ATO, especially at 5 lM concentration, which was evi- dent from decreased activity of lactate dehydrogenase (5 lM ATO ? 20 lg/mL BDE: 6.61 ± 1.97 lU/mL, respective control group: 16.15 ± 1.92 lU/mL), reduced oxidative stress, calcium influx and organelle damage. Results obtained from the present study allow for a better characterization of the effects of ATO on H9c2 myoblasts. In conclusion, our data suggest that cell organelles are also the targets of ATO-induced cardiotoxicity in addition to other reported targets like ion channels, and BDE has the potential to protect the cardiotoxicity induced by ATO. Keywords Arsenic trioxide Á Boerhavia diffusa Á H9c2 Á Intracellular calcium Á Mitochondria Á Oxidative stress Abbreviations APD20 Action potential duration at 20 % of repolarization APL Acute promyelocytic leukaemia ATO Arsenic trioxide BDE Ethanolic extract of Boerhavia diffusa CAT Catalase ECG Electrocardiograph ER Endoplasmic reticulum LDH Lactate dehydrogenase NR Neutral red ROS Reactive oxygen species SOD Superoxide dismutase Introduction Arsenic trioxide (ATO) is a very potent antitumor agent used to treat acute promylocytic leukaemia (APL) patients who acquire resistance to all-trans retinoic acid therapy [1, 2]. Clinical use of ATO is restricted due to its toxicity profile that includes cardiotoxicity [3] and certain other organ toxicity [4]. Cardiotoxicity associated with ATO ranges from electrocardiographical (ECG) changes and temporary left ventricular ejection fraction decline to congestive heart failure [3]. The major ECG lesions include QT prolongation and torsedes de pointes. The mechanisms of anticancer activity of ATO include induction of apop- tosis mediated by reactive oxygen species (ROS) and excessive intracellular calcium ([Ca 2? ]i) influx [5–7]. V. P. Vineetha Á A. Prathapan Á R. S. Soumya Á K. G. Raghu (&) Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, Kerala, India e-mail: raghukgopal2009@gmail.com 123 Cardiovasc Toxicol DOI 10.1007/s12012-012-9191-x