title: 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.
authors.affiliation: Agroprocessing and Natural Products Division, Council of Scientific and Industrial Research-National Institute for Interdisciplinary Science and Technology (CSIR-NIIST), Thiruvananthapuram 695019, Kerala, India.
authors.forename: V P
authors.initials: VP
authors.lastname: Vineetha
authors.forename: A
authors.initials: A
authors.lastname: Prathapan
authors.forename: R S
authors.initials: RS
authors.lastname: Soumya
authors.forename: K G
authors.initials: KG
authors.lastname: Raghu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000037:antagonists & inhibitors; D020013:Calcium Signaling / Q000187:drug effects; D009202:Cardiomyopathies / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032386:Myoblasts, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D039281:Nyctaginaceae / Q000737:chemistry*; D015388:Organelles / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000077237:Arsenic Trioxide