Therapeutic effect of quercetin on the complications of nicotinamide-streptozotocin induced type-2 diabetes in male rats

Abstract

Introduction: Type-2 diabetes mellitus (T2DM) is a rapid growing epidemic disease, with a continuous increasing prevalence that exhibit complications in different body organs.  The nicotinamide-streptozotocin (NA-STZ) rat model induces similar conditions to T2DM in humans, therefore used for studying the drugs and natural products effects on diabetic complications.Aim: This study was performed in order to investigate the therapeutic; biochemical effects of the flavonoid compound quercetin (Q) to treat the complications, with a glance at the testicular dysfunction of type-2 diabetes induced by nicotinamide-streptozotocin (NA–STZ) in male rats.  Methods: Type-2 diabetes was induced in fasted rats by an intraperitoneal (ip) injection of STZ (100 mg/kg b. wt.; freshly prepared in citrate buffer, pH 4.5), after 15 min of nicotinamide administration (NA) (240 mg/kg b. wt.).  The rats were divided into the following groups (10 animals / group): Group 1: Control group, Group 2: (quercetin treated rats; Q group): Rats were given quercetin (100 mg/kg), Group 3: (NA-STZ treated group or diabetic (D) group) and Group 4: (NA-STZ/quercetin treated group; DQ).  After 30 days, the animals were fasted overnight, sacrificed, then the blood was collected, the serum was separated,  Epididymal sperm number (ESN) was collected and the testes of each animal were excised and then stored at -80oC. Results:  Oral supplementation of quercetinsignificantly (p<0.05) ameliorated the glucose level in T2DM rats.  Further, quercetin treatment of T2DM rats significantly ameliorated the total cholesterol, triglycerides, total proteins, albumin, urea, creatinine levels, liver transaminases (ALT, AST), alkaline phosphatase and gamma glutamyl transpeptidase activities.  Furthermore, quercetin administrationsignificantly enhanced serum level of insulin, testosterone, follicle-stimulating hormone and luteinizing hormone.  Additionally, quercetin administration improved the antioxidant status in the testicular tissues of T2DM rats, by enhancing the superoxide dismutase, glutathione peroxidase, catalase, acetylcholinestrase and butrylcholinestrase activities in parallel with decline the malondialdehyde nitric oxide, the pro-inflammatory markers; interleukin-6, tumor necrosis factor-alpha, nuclear factor kappa-B levels and up-regulated the relative ratio of Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) gene expression.  Conclusion: Quercetin has potential therapeutic effects on different complications of T2DM induced nicotinamide-streptozotocin in male rats. Quercetinimproved testicular dysfunctions in T2DM, which is mediated by improving of the testicular antioxidant, anti-inflammatory status, acetylcholinestrase and butrylcholinestrase activities, also up-regulation of the PPAR-γ gene expression.  Therefore, regular daily administration of quercetin is recommended to regulate the different complications of T2DM and to decrease risk of infertility in men.

Keywords:Quercetin, antidiabetic, testicular dysfunction, nicotinamide-streptozotocin, Peroxisome Proliferator-Activated Receptor-γ gene expression.