Arsenic Trioxide Toxicity in H9c2 Myoblasts—Damage to Cell Organelles and Possible Amelioration with Boerhavia diffusa

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.

Salvianolic Acid A Protects H9c2 Cells from Arsenic Trioxide-Induced Injury via Inhibition of the MAPK Signaling Pathway

“…Decreased ΔΨm implies membrane depolarization and can trigger mitochondrion-dependent apoptosis. Consistent with previous work [17], the present study showed that ΔΨm decreased in ATO-treated cells, as shown by the fluorescence shift from the upper left to lower right of the panel. As shown in Fig.…”

“…ATO exerts a rapid noxious effect on mitochondria [17]. Decreased ΔΨm implies membrane depolarization and can trigger mitochondrion-dependent apoptosis.…”

Phloretin ameliorates arsenic trioxide induced mitochondrial dysfunction in H9c2 cardiomyoblasts mediated via alterations in membrane permeability and ETC complexes

“…There are reports on the adverse effects of ATO on cardiac tissue , adult cardiac myocytes (Raghu and Cherian, 2009) and cardiac cell line (Vineetha et al, 2013) from our group as well as from other groups (Zhou et al, 2003). Oxidative stress and associated complications like inhibition of cardiac ion channels are reported to be the main pathological mechanisms responsible for cardiotoxicity.…”

Arsenic and the Cardiovascular System

“…However, treating these rats with aqueous extract of C. olitorius leaves 15 days prior to NaAsO 2 administration protected their cardiac tissue from As-induced cardiotoxicity by maintaining the activities of the aforementioned enzymes. Ethanolic extract of Boerhavia diffusa (BDE) was also found to protect H9c2 myoblasts against ATO-induced cardiotoxicity [130]. In this study, ATO treatment at varying concentrations (5, 7.5, and 10 μM) reduced the integrity of mitochondria, initiated ER stress, disrupted cytoskeletal networks, inhibited antioxidant enzymes, and increased both ROS generation and Ca 2+ load.…”