International Science Community Association International Research Journal of Biological Sciences 14 4 2025 11 10 Ebselen Mitigates Methylmercury-Induced Nephrotoxicity in NRK52E Cells 18 26 EN Khyade Vitthalrao Bhimasha 1 Department of Zoology, Sharadabai Pawar Mahila Arts, Commerce and Science College, Shardanagar Tal. Baramati Dist. Pune – 413115, India Khanapure Nikhil Pandit 2 Department of Chemistry, Punyashlok Ahilyadevi Holkar Solapur University, Solapur, Maharashtra-413 255, India . Shilpa 1 Department of Zoology, SSJDWSSS GPG College Ranikhet–263645, Uttarakhand, India Pandey Deepa 2 Department of Zoology, SSJDWSSS GPG College Ranikhet–263645, Uttarakhand, India Kumar Shankar 3 Department of Mathematics, SSJDWSSS GPG College Ranikhet–263645, Uttarakhand, India Gupta Pragati Kumari 1 Department of Zoology, Maharani Janki Kunwar College, Bettiah, West Champaran, Bihar-845438, India . Hafizurrahman 2 Department of Zoology, Maharani Janki Kunwar College, Bettiah, West Champaran, Bihar-845438, India > Research Paper 2025 8 10 2025 11 10 Mercury, a toxic environmental pollutant, is readily available in the biogeochemical cycle and poses serious health risks even at trace levels due to its tendency to bioaccumulate. Among its forms, methylmercury (MeHg) is the most toxic, capable of crossing both the placental barrier and blood-brain barrier. This study investigates the cellular toxicity of MeHg on normal rat kidney epithelial cells (NRK52E) and evaluates the protective potential of Ebselen, an organic selenium compound with antioxidant and metal-chelating properties. NRK52E cells were exposed to 0.5 µM, 1 µM, 5 µM and 10 µM concentrations of MeHg, both alone and in combination with 10 µM Ebselen. Multiple assays including MTT for cell viability, wound healing for cell migration, DCFDA for reactive oxygen species (ROS), real-time PCR for gene expression, and cell cycle analysis were performed to assess the extent of toxicity and protection. MeHg exposure led to a significant increase in ROS levels, accompanied by dysregulation of key oxidative stress and cell cycle-related genes such as cMYC, HIF-1α, VEGF, and MMP9. These molecular changes were associated with disrupted cell behaviour, impaired wound healing, and altered cell cycle progression, all indicating cellular toxicity. However, co-treatment with Ebselen significantly reversed these effects. ROS levels were reduced, gene expression patterns normalized, and cell cycle distribution improved. Ebselen’s ability to restore cellular homeostasis demonstrates its strong protective effect against MeHg-induced nephrotoxicity. This study highlights the potential of Ebselen as a therapeutic agent for mitigating mercury-induced kidney cell damage. It emphasizes the importance of early detection of nephrotoxic effects and timely antioxidant intervention to prevent long-term renal impairment caused by environmental toxins like MeHg. Copyright@ International Science Community Association