Naringenin neutralises oxidative stress and nerve growth factor discrepancy in experimental diabetic neuropathy

Abstract

Objectives: Present study aims to investigate the ameliorative effects of naringenin (NG) on experimentally induced diabetic neuropathy (DN) in rats. Methods: Diabetes was induced by single intraperitoneal injection of streptozotocin (STZ, 60 mg/kg). Naringenin (25 and 50 mg/kg/day) treatment was started 2 weeks after the diabetes induction and continued for five consecutive weeks. Pain threshold behaviour tests were performed at the end of the treatment. Serum levels of glucose, insulin and pro-inflammatory cytokines were assessed. In sciatic tissues, markers oxidative stress, cytokines and neurotrophic factors were measured. Results: NG treatments showed significant decrease in paw-withdrawal (P< 0.01) and tail-flick latency (P< 0.01). The drug attenuated the diabetic-induced changes in serumglucose, insulin and pro-inflammatory cytokines including tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6). In sciatic nerve, the diabetic-induced alterations in interleukins and oxidative stress biomarkers were significantly attenuated by NG. Decreased sciatic expressions of insulin growth factor (IGF) and nerve growth factor (NGF) in diabetic rats were also ameliorated by NG. Diabetes-induced dysregulated levels of nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were ameliorated byNG. Histological analysis showed thatNGcorrected the altered sciatic changes in diabetic animals. Discussion:Wesuggest that neuro-protective effect ofNGmolecules in sciatic nerve of diabetic rats, through its anti-diabetic as well as antioxidant and anti-inflammatory properties.