Ameliorative effect of naringenin on hyperglycemia-mediated inflammation in hepatic and pancreatic tissues of Wistar rats with streptozotocin- nicotinamide-induced experimental diabetes mellitus

Abstract

In diabetes mellitus (DM), sustained hyperglycemia results in the generation of reactive oxygen species, ultimately leading to increased oxidative stress and inflammation in vital tissues. In the present study, possible ameliorative effects of naringenin on hyperglycemia-mediated inflammation in experimental streptozocin (STZ)-nicotinamide-induced DM were sought. DM was induced experimentally in overnight-fasted Wistar rats (150-180 g) by intra-peritoneal injection of STZ (50 mg/kg.b.w) and of nicotinamide (110 mg/kg.b.w); control rats (n = 6) received only vehicle (0.5 ml of 0.1 M of cold citrate buffer; pH 4.5). One group of diabetic rats (n = 6) was left untreated while another group of diabetic rats (n = 6) received naringenin (50 mg/kg b.w./day) orally for 21 days. At this time, hemotological indices (erythrocyte sedimentation rate [ESR], total white blood cell [WBC] count, differential WBC percentage, and platelet count) were measured. Significant alterations in expression of gene and protein biomarkers of inflammation in hepatic and pancreatic tissues were determined by measuring mRNA levels and the level of protein expressed, respectively, as was the total nitric oxide level in these tissues. Diabetic rats showed significantly higher mean ESR values, total WBC counts, differential WBC percentages, and platelet counts than those in control rats; similarly, mean mRNA levels of C-reactive protein, pro-inflammatory cytokine, nuclear factor-κB and inducible nitric oxide synthase genes and mean intensities of expression of the corresponding proteins in the hepatic and pancreatic tissue samples from diabetic rats significantly exceeded those in control rats. However, in diabetic rats treated with naringenin, the values of hematological, mRNA transcript and protein indices of inflammation were all lower than those in diabetic rats. These results suggest that naringenin possibly alleviates hyperglycemia-mediated inflammation in experimental STZ-nicotinamide-induced DM in Wistar rats.