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

Abstract

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.