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

Abstract

BackgroundInsulin 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.ObjectivesThe study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo.MethodsMale 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.ResultsAtazanavir (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.ConclusionNaringin prevents PI-induced glucose intolerance and impairment of insulin signaling and as nutritional supplement it could therefore alleviate metabolic complications associated with antiretroviral therapy.

Integrated Metabolomic and Transcriptomic Analysis of the Flavonoid Accumulation in the Leaves of Cyclocarya paliurus at Different Altitudes

“…Flavonoids function as antioxidants by reducing DNA damage caused by reactive oxygen species accumulation. Naringin is a flavanone that exhibits antioxidant, antidiabetic, anti-dyslipidemic, and anti-inflammatory activities ( Vinayagam and Xu, 2015 ; Nzuza et al, 2017 ). Tricetin is a potential anti-inflammatory and anticancer agent ( Chang et al, 2017 ; Chung et al, 2017 ).…”

Sirtuins as Interesting Players in the Course of HIV Infection and Comorbidities

“…Studies on male Wistar rats orally treated with SQV (333 mg/kg/day) or ATV (133 mg/kg/day) showed significantly reduced levels of pancreatic ATP compared to the control group. Pancreatic UCP2 expression was instead increased in the ATV-and SQV-treated group compared to the control [77]. The above data may indicate the existence of a potential mechanism involving SIRT1, which can be considered to prevent drug-induced negative changes in HIV-infected patients.…”

Protective and Ameliorative Effects of Hydroethanolic Extract of Piper nigrum (L.) Stem against Antiretroviral Therapy-Induced Hepatotoxicity and Dyslipidemia in Wistar Rats

“…NRTIs and PIs have been demonstrated to impair adipocyte function, lipid metabolism, and glucose metabolism. These drugs inhibit adipocyte differentiation as well as adiponectin expression, secretion, and release from adipose tissues [ 66 , 67 ]. Adiponectin plays an important role in glucose regulation and fatty acid oxidation [ 67 ].…”

“…Tis result is supported by the fact that ART is associated with lipoatrophy (loss of fat tissues) [66]. NRTIs and PIs have been demonstrated to impair adipocyte function, lipid metabolism, and glucose metabolism.…”