A Mechanistic Approach for Modulation of Arsenic Toxicity in Human Lymphocytes by Curcumin, an Active Constituent of Medicinal Herb Curcuma longa Linn

Abstract

Summary Chronic exposure of humans to high concentrations of arsenic in drinking water is associated with skin lesions, peripheral vascular disease, hypertension, blackfoot disease and a high risk of cancer. Arsenic induces single strand breaks, DNA-protein crosslinks and apurinic sites in DNA, which are prerequisites for induction of cancer. Amelioration of such damages with natural compounds could be an effective strategy to combat arsenic toxicity. Curcumin is the active ingredient of turmeric, a common household spice, which is a rich source of polyphenols and this compound has been extensively studied as a chemopreventive agent against many types of cancer. The present study investigates whether curcumin could counteract the DNA damage caused by arsenic as assessed by single cell gel electrophoresis (SCGE) using peripheral blood lymphocytes, from healthy donors. It was observed that DNA damage induced by arsenic could be efficiently reduced by curcumin and the effect was more pronounced when lymphocytes were pre-incubated with curcumin prior to arsenic insult. Arsenic caused DNA damage by generation of reactive oxygen species (ROS) and enhancement of lipid peroxidation levels. Curcumin counteracted the damage by quenching ROS, decreasing the level of lipid peroxidation and increasing the level of phase II detoxification enzymes like catalase, superoxide dismutase and glutathione peroxidase. Curcumin also enhanced the DNA repair activity against arsenic induced damage. The expression of polymerase, a repair enzyme, was found to be highly elevated when arsenite induced damaged cells were allowed to repair in presence of curcumin. Results indicate that curcumin has significant role in confronting the deleterious effect caused by arsenic, which could be an economic mode of arsenic mitigation among rural population in West Bengal, India.

miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

“…SCGE assays were performed according to the method of Mukherjee et al [14]. The results were visualized under DM6000B fluorescence microscope (Leica, Germany).…”

Tumor-suppressive effects of miR-29c on gliomas

“…Comet was assayed using the method of Mukherjee et al [13]. Briefly, slides were stained with ethidium bromide and examined under a fluorescence microscope and subjected to image analysis using the comet assay software program.…”

Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice

“…Association of arsenic intoxication with cancer, black foot disease and diabetes has also been reported [18,19]. Arsenic exposure in mice has been found to be associated with the increased free radical generation that affects the primary electron rich sites within the cells and cause DNA damage in human lymphocytes [20-22], breaking of DNA strand, DNA base modifications, protein crosslink, structural carbohydrates and lipids [23-25]. Arsenic induced cell death has been strongly linked to the induction of autophagy in human lymphoblastoid cell lines to impart its immunotoxic effects [11,12].…”