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Lead‐induced DNA damage and cell apoptosis in human renal proximal tubular epithelial cell: Attenuation via N‐acetyl cysteine and tannic acid
Authors:Manushi Siddarth  Diwesh Chawla  Alpana Raizada  Neelam Wadhwa  Basu D Banerjee  Meera Sikka
Institution:1. Multidisciplinary Research Unit, University College of Medical Sciences (University of Delhi) and G. T. B. Hospital, Delhi, India;2. Department of Medicine, University College of Medical Sciences (University of Delhi) and G. T. B. Hospital, Delhi, India;3. Department of Pathology, University College of Medical Sciences (University of Delhi) and G. T. B. Hospital, Delhi, India;4. Department of Biochemistry, University College of Medical Sciences (University of Delhi) and G. T. B. Hospital, Delhi, India
Abstract:This study investigates the exposure of lead‐induced reactive oxygen species (ROS) generation, DNA damage, and apoptosis and also evaluates the therapeutic intervention using antioxidants in human renal proximal tubular cells (HK‐2 cells). Following treatment of HK‐2 cells with an increasing concentration of lead nitrate (0–50 μM) for 24 h, the intracellular ROS level increased whereas the GSH level decreased significantly in a dose‐dependent manner. Comet assay results revealed that lead nitrate showed the ability to increase the levels of DNA strand breaks in HK‐2 cells. Lead exposure also induced apoptosis through caspase‐3 activation at 30 μg/mL. Pretreatment with N‐acetylcysteine (NAC) and tannic acid showed a significant ameliorating effect on lead‐induced ROS, DNA damage, and apoptosis. In conclusion, lead induces ROS, which may exacerbate the DNA damage and apoptosis via caspase‐3 activation. Additionally, supplementation of antioxidants such as NAC and tannic acid may be used as salvage therapy for lead‐induced DNA damage and apoptosis in an exposed person.
Keywords:antioxidants  apoptosis  DNA damage  HK‐2 cells  lead nitrate  ROS generation
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