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 deposi… Show more
“…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.…”
Section: Discussionmentioning
confidence: 49%
“…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.…”
Section: Discussionmentioning
confidence: 62%
“…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.…”
The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on AsO therapy.
“…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.…”
Section: Discussionmentioning
confidence: 49%
“…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.…”
Section: Discussionmentioning
confidence: 62%
“…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.…”
The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on AsO therapy.
“…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.…”
Section: Potential Anti-leukemia Activity Of Pvlmentioning
“…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.…”
Arsenic trioxide (ATO) resistance is a challenging problem in chemotherapy. However, the underlying mechanisms remain to be elucidated. In this study, we identified a high level of expression of miR-155 in a human lung adenocarcinoma A549R cell line that is highly resistant to ATO. We showed that the high level of miR-155 was associated with increased levels of cell survival, colony formation, cell migration and decreased cellular apoptosis, and this was mediated by high levels of Nrf2, NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1) and a high ratio of Bcl-2/Bax. Overexpression of the miR-155 mimic in A549R cells resulted in increased levels of colony formation and cell migration as well as reduced apoptosis along with increased Nrf2, NQO1 and HO-1. In contrast, silencing of miR-155 expression with its inhibitor in the cells, significantly decreased the cellular levels of Nrf2, NQO1 and HO-1 as well as the ratio of Bcl-2/Bax. This subsequently reduced the level of colony formation and cell migration facilitating ATO-induced apoptosis. Our results indicate that miR-155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells. Our study provides new insights into miR-155-mediated ATO resistance in lung cancer cells.
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