title: Naringin protects against HIV-1 protease inhibitors-induced pancreatic β-cell dysfunction and apoptosis.
abstract: The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic β-cells and apoptosis were investigated in RIN-5F cells in culture.
  
  
  
  Cells in culture medium were challenged with 11-25 mM glucose with or without nelfinavir (1-10 μM), saquinavir (1-10 μM) and atazanavir (5-20 μM), respectively for 24 h to determine insulin secretion. The cells were further treated with nelfinavir (10 μM), saquinavir (10 μM), atazanavir (20 μM) with and without naringin or glibenclamide (10 μM) for 24 h to determine insulin secretion, lipid peroxidation, Superoxide Dismutase (SOD) activity, glutathione (GSH) levels, ATP production and caspase-3 and-9 activities, respectively.
  
  
  
  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.
  
  
  
  PIs impair β-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 β-cell dysfunction and the attendant metabolic complications caused by PIs in patients on antiretroviral therapy.
authors: Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, P.O. Box X5401, Durban, South Africa.
authors: Sanelisiwe
authors: S
authors: Nzuza
authors: Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, P.O. Box X5401, Durban, South Africa.
authors: Duduzile E
authors: DE
authors: Ndwandwe
authors: Molecular and Clinical Pharmacology Research Laboratory, Department of Pharmacology, Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, P.O. Box X5401, Durban, South Africa. Electronic address: owirap@ukzn.ac.za.
authors: Peter M O
authors: PMO
authors: Owira
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D044950:Flavanones / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D016333:HIV Protease / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000009:adverse effects*; D020128:Inhibitory Concentration 50; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D044950:Flavanones; D017320:HIV Protease Inhibitors; D007328:Insulin; D020011:Protective Agents; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D000255:Adenosine Triphosphate; D013482:Superoxide Dismutase; D053148:Caspase 3; D053453:Caspase 9; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1; D005978:Glutathione; D005947:Glucose; C005274:naringin
keywords: Antioxidants; Glibenclamide; HIV protease inhibitors; Insulin; Naringin