Naringin protects against HIV-1 protease inhibitors-induced pancreatic β-cell dysfunction and apoptosis

Introduction: The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic beta-cells and apoptosis were investigated in RIN-5F cells in culture. Methods: Cells in culture medium were challenged with 11-25 mM glucose with or without nelfinavir (1-10 mu M), saquinavir (1-10 mu M) and atazanavir (5-20 mu M), respectively for 24 h to determine insulin secretion. The cells were further treated with nelfinavir (10 mu M), saquinavir (10 mu M), atazanavir (20 mu M) with and without naringin or glibenclamide (10 mu M) for 24 h to determine insulin secretion, lipid per oxidation, Superoxide Dismutase (SOD) activity, glutathione (GSH) levels, ATP production and caspase-3 and -9 activities, respectively. Results: Glucose-dependent insulin secretion was significantly reduced by PIs in a concentration dependent manner. Treatment with either naringin or glibenclamide significantly reduced lipid peroxidation, Superoxide Dismutase (SOD) activities and also increased glutathione (GSH) and ATP levels in the cells that were treated with PIs. Furthermore, naringin or glibenclamide significantly reduced caspase-3 and caspase-9 activities in cells that were treated with PIs. Conclusions: Pls impair beta-cell functions by increasing oxidative stress and apoptosis. Treatment with naringin protected RIN-5F cells from PI-induced oxidative damage and apoptosis. Our results therefore suggest that nutritional supplements with naringin could prevent pancreatic beta-cell dysfunction and the attendant metabolic complications caused by PIs in patients on antiretroviral therapy. (C) 2016 Elsevier Ireland Ltd. All rights reserved.