By reducing oxidative stress, naringenin mitigates hyperglycaemia-induced upregulation of hepatic nuclear factor erythroid 2-related factor 2 protein

Abstract

Objectives: Antioxidant and anti-inflammatory properties of naringenin could confer hepatoprotective effects. Methods: Chang cells in culture media were maintained at 37°C and treated with increased concentrations of glucose (5.5–50 mm) and/or naringenin (25–100 µm), respectively, for 24 h. The cells were harvested and carbonyl proteins, antioxidant enzymes and proteins measured in cell lysates. Sprague Dawley rats were divided into 5 groups (n = 7) and orally treated daily for 56 days with 3.0 ml/kg per body weight (BW) distilled water (group 1), 60 mg/kg BW of naringenin (groups 2 and 4), respectively. Groups 3, 4 and 5 were given single 60 mg/kg per BW intraperitoneal injections of streptozotocin or insulin (2.0 IU/kg BW bid), (group 5 only). Key findings: Cell viability was significantly decreased in response to increased hyperglycaemia but naringenin dose-dependently, significantly reversed this compared to controls, respectively. However, antioxidant enzyme activities were reduced due to increased and reduced oxidative stress, respectively. Naringenin further significantly reduced hepatic oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression and liver : body weight ratios in diabetic compared to controls rats. Conclusions: Naringenin confers hepatoprotective antioxidant effects by initially preventing upregulation of Nrf2 protein expression and its downstream antioxidant enzymes.