In Vitro Evidences for Renal-Protective Properties of Phloretin in Nephrotoxicity Induced by Bisphenol-A via Mediation of VCAM-1/ICAM-1 Genes Expression

Abstract

Background: Oxidative stress is a major contributor to kidney dysfunction. Phloretin, a dietary flavonoid, exhibits antioxidant and anti-inflammatory activity. This study evaluated the protective effects of Phloretin against Bisphenol-A (BPA)-induced oxidative stress in human renal tubular epithelial (HK-2) cells. Methods: HK-2 cells were exposed to BPA (1000 μM) for 24 hr with or without Phloretin (50, 100, 200 μM). Cell viability, oxidative stress markers Reactive Oxygen Species (ROS), Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), cytokines (IL-6, IL-10), and VCAM-1/ICAM-1 expression were assessed. Results: BPA markedly decreased cell viability and TAC while elevating ROS, MDA, IL-6, and VCAM-1/ICAM-1 expression (all p<0.001). Phloretin significantly reversed these effects in a dose-dependent manner. At 200 μM, Phloretin increased cell viability by ~35–40% (p<0.001), reduced ROS and MDA by ~35–40% (p<0.001), and restored TAC by ~40–45% (p<0.001) compared to BPA. Inflammatory markers were also modulated: IL-6 was reduced by ~35–40% (p<0.001), while IL-10 was elevated by ~40–45% (p<0.001). Moreover, Phloretin suppressed VCAM-1 and ICAM-1 expression by ~45–50% (p<0.001). Conclusion: Phloretin significantly attenuates BPA-induced oxidative stress and inflammation in renal tubular cells, suggesting its potential as a natural nephroprotective agent.