Omega-3 Fatty Acid Protects Against Arsenic Trioxide-Induced Cardiotoxicity In Vitro and In Vivo

Abstract

Arsenic trioxide (AsO) is a highly effective therapeutic against acute promyelocytic leukaemia, but its clinical efficacy is burdened by serious cardiac toxicity. The present study was performed to evaluate the effect of omega (ω)-3 fatty acid on AsO-induced cardiac toxicity in in vivo and in vitro settings. In in vivo experiments, male Wistar rats were orally administered with AsO 4 mg/kg body weight for a period of 45 days and cardiotoxicity was assessed. AsO significantly increased the tissue arsenic deposition, micronuclei frequency and creatine kinase (CK)-MB activity. There were a rise in lipid peroxidation and a decline in reduced glutathione, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and catalase in heart tissue of arsenic-administered rats. The cardioprotective role of ω-3 fatty acid was assessed by combination treatment with AsO. ω-3 fatty acid co-administration with AsO significantly alleviated these changes. In in vitro study using H9c2 cardiomyocytes, AsO treatment induced alterations in cell viability, lactate dehydrogenase (LDH) release, lipid peroxidation, cellular calcium levels and mitochondrial membrane potential (∆Ψ). ω-3 fatty acid co-treatment significantly increased cardiomyocyte viability, reduced LDH release, lipid peroxidation and intracellular calcium concentration and improved the ∆Ψ. These findings suggested that the ω-3 fatty acid has the potential to protect against AsO-induced cardiotoxicity.

Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats

“…In hyperglycemia also, FSO supplementation significantly reduced LPO and increased the GSH content, and thereby alleviated the membrane dysfunction of human erythrocytes [23]. The use of FSO is a very cost effective approach than DHA in alleviating the cardiotoxicity of As 2 O 3 [7]. In the current investigation, FSO treatment increased the activities of antioxidant enzymes and total thiol levels in cardiac tissues, suggesting the improved antioxidant defense in cardiac tissues.…”

“…Our observation also support above fact as evidenced from increased levels of cardiac marker enzymes CK-MB and LDH in the serum of As 2 O 3 alone treated rats. Omega-3 fatty acid in FSO may have a significant role in cardiac protection by improving the antioxidant status and the effective arsenic removal [7]. In the current investigation, treatment with FSO reduced As 2 O 3 toxicity possibly by reducing the oxidative stress and the arsenic deposition.…”

“…But the use of As 2 O 3 is hampered by its cardiotoxicity characterized by action potential variations, QT interval prolongation, torsades de pointes and even sudden cardiac death [5,6]. Enhanced oxidative stress in cardiac tissue due to arsenic deposition was a major etiology of arsenicinduced cardiotoxicity [7]. Now a day, dietary supplements in the form of functional foods/nutraceuticals has been receiving lots of attention in the mitigation of cardiotoxicity induced by chemotherapeutic drugs.…”

Is LukS-PV a novel experimental therapy for leukemia?

“…As long as we could well control the dose, the poison might become an anti-cancer agent. Furthermore, toxins could be appropriately designed or combined with other drugs to reduce toxicity (Tan et al, 2012;Fan et al, 2014;Varghese et al, 2016). Therefore, the anti-leukemia activity of PVL will become a research hotspot in our future study.…”

miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells

“…However, the doses for ATO to induce lung cancer cell death are much higher than those for the treatment of hematologic malignancies 6 – 8 , indicating that lung cancer cells are more resistant to ATO than hematologic cancer cells. Since a high dose of ATO can result in severe side effects 9 , this hinders the preclinical trials of ATO for lung cancer treatment. Thus, it is critically important to study the mechanisms underlying ATO resistance of lung cancer cells as this will help identify novel targets for attenuating ATO resistance, thereby facilitating the application of ATO as a new treatment for lung cancer.…”