Arsenic trioxide (AsO) is a potent drug for the treatment of acute promyelocytic leukemia (APL) and has achieved remarkable remissions in patients. Unfortunately, clinical reports have shown that the treatment is associated with cardiotoxicity. Many efforts have been made to mitigate drug-mediated cardiac damage using naturally occurring antioxidant compounds possessing free radical scavenging activity. The present investigation aims to explore protective role of L-ascorbic acid (L-AA) and α-tocopherol (α-TOC) from AsO-induced oxidative stress in H9c2 cardiomyocytes through the evaluation of Nrf2 (nuclear factor erythroid 2-related factor 2) and Bcl-2 (B-cell lymphoma 2) transcription factors. The in vitro study was conducted using H9c2 cardiomyocytes. The evaluation of total antioxidant capacity, mitochondrial membrane potential, cellular calcium concentration and reactive oxygen species generation was performed. Oxidative stress (Nrf2) and anti-apoptotic (Bcl2) signaling indicators were measured by reverse transcriptase polymerase chain reaction. A depletion of the total antioxidant capacity and mitochondrial transmembrane potential were observed in AsO-treated cardiomyocytes. In addition, the cellular calcium concentration and ROS generation were found to be increased on treatment with AsO with the alterations in the activity of transcription factors, Nrf2 and Bcl2. Co-treatment of antioxidant vitamins with AsO resulted in a significant reversal of oxidative stress and alteration on the antioxidant defense through the activation of Nrf2 and Bcl2. L-AA and α-TOC alleviates AsO-induced oxidative stress in cardiac cells by activating Nrf2 and Bcl2 transcription factors that results in increased cell survival and prevents apoptosis.
Arsenic trioxide (AsO) is a promising new regimen for the treatment of acute promyelocytic leukemia (APL). The induction of oxidative stress mediated by reactive oxygen species (ROS) and excessive intracellular calcium influx are the main reasons behind AsO toxicity. Since liver is the major organ for xenobiotic metabolism, it is always under stress. Antioxidant vitamins such as L-Ascorbic acid (L-AA) and α-Tocopherol (α-TOC) have been proposed to have beneficial effects against a variety of pathological conditions and are known by their free radical scavenging properties. The present study evaluates the curative efficacy of L-AA and α-TOC against AsO toxicity using immortalized human Chang liver cells. Our results suggest that L-AA (100 µM) and α-TOC (50 µM) recovered AsO (10 µM) cytotoxicity. Furthermore, AsO treatment showed an increase in lipid peroxidation and depletion in antioxidant status, mitochondrial trans membrane potential and values of total antioxidant capacity. Cotreatment of antioxidant vitamins with AsO resulted in a significant reversal of oxidative stress markers. Our findings substantiate the effect of antioxidant vitamins in protecting the hepatocytes from oxidative stress which may be attributed through Nrf2 (Nuclear factor erythroid 2-related factor 2) mediated upregulation of Bcl2 (B-cell lymphoma 2) expression.
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