Naringin prevents HIV-1 protease inhibitors-induced metabolic complications in vivo.

BACKGROUND: Insulin resistance, glucose intolerance and overt diabetes are known metabolic complications associated with chronic use of HIV-Protease Inhibitors. Naringin is a grapefruit-derived flavonoid with anti-diabetic, anti-dyslipidemia, anti-inflammatory and anti-oxidant activities. OBJECTIVES: The study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo. METHODS: Male Wistar rats were divided into six groups (n = 6) and were daily orally treated with distilled water {3.0 ml/kg body weight (BW)}, atazanavir (133 mg/kg BW), saquinavir (333 mg/kg BW) with or without naringin (50 mg/kg BW), respectively for 56 days. Body weights and water consumption were recorded daily. Glucose tolerance tests were carried out on day 55 of the treatment and thereafter, the rats were sacrificed by halothane overdose. RESULTS: Atazanavir (ATV)- or saquinavir (SQV)-treated rats exhibited significant weight loss, polydipsia, elevated Fasting blood glucose (FBG), reduced Fasting Plasma Insulin (FPI) and expression of phosphorylated, Insulin Receptor Substrate-1 (IRS-1) and Akt proteins, hepatic and pancreatic glucokinase levels, and also increasing pancreatic caspase-3 and -9 as well as UCP2 protein expressions compared to controls, respectively. These effects were completely reversed by naringin treatment. CONCLUSION: Naringin prevents PI-induced glucose intolerance and impairment of insulin signaling and as nutritional supplement it could therefore alleviate metabolic complications associated with antiretroviral therapy.

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

INTRODUCTION: The protective effects of grapefruit-derived naringin against HIV-1 Protease Inhibitors (PIs)-associated oxidative damage to pancreatic ß-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 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. 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: PIs impair ß-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 ß-cell dysfunction and the attendant metabolic complications caused by PIs in patients on antiretroviral therapy.