Cardiovascular Toxicology

, Volume 13, Issue 2, pp 123–137

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
Article

DOI: 10.1007/s12012-012-9191-x

Cite this article as:
Vineetha, V.P., Prathapan, A., Soumya, R.S. et al. Cardiovasc Toxicol (2013) 13: 123. doi:10.1007/s12012-012-9191-x

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 protective 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 μM) on cell organelles like mitochondria, endoplasmic reticulum (ER), lysosome and actin, generation of reactive oxygen species, antioxidant enzyme status and intracellular calcium overload were evaluated. ATO significantly (P ≤ 0.05) altered mitochondrial transmembrane potential, intracellular calcium 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 μM concentration, which was evident from decreased activity of lactate dehydrogenase (5 μM ATO + 20 μg/mL BDE: 6.61 ± 1.97 μU/mL, respective control group: 16.15 ± 1.92 μU/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 trioxideBoerhavia diffusaH9c2Intracellular calciumMitochondriaOxidative 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

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • V. P. Vineetha
    • 1
  • A. Prathapan
    • 1
  • R. S. Soumya
    • 1
  • K. G. Raghu
    • 1
  1. 1.Agroprocessing and Natural Products DivisionCouncil of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST)ThiruvananthapuramIndia