Background: Diabetes mellitus (DM) is a metabolic disorder that occurs as a result of absolute or relative insufficiency of insulin release and/or insulin effect due to impairment of carbohydrate, fat and protein metabolism, and it is characterized by hyperglycemia and leads to various complications. Objective: In this study, it was aimed to investigate the effects of hesperidin (HP) and quercetin, which are natural flavonoids, on serum malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6) levels in rats with streptozotocin (STZ)-induced diabetes. Materials and Methods: The experimental animals were divided into four groups, each group comprising ten rats designated as follows: Group 1 served as control rats (C); Group 2 served as diabetic rats (DM); Group 3 served as diabetic rats administered HP (DM + HP) (100 mg/kg b. w.); and Group 4 served as diabetic rats administered quercetin (DM + Q) (100 mg/kg b. w.). Results: Serum MDA and GSH levels were significantly higher in STZ-induced DM group than control group (P < 0.05). In DM + HP and DM + Q groups, MDA levels were significantly decreased compared to DM groups (P < 0.05), but there was no significant difference GSH levels between DM, DM + HP, and DM + Q groups (P > 0.05). TNF-α levels in STZ-induced DM group were significantly decreased compared to control group (P < 0.05), and groups of DM + HP and DM + Q had higher serum TNF-α levels than STZ-induced DM group (P < 0.05). In STZ-induced DM group, serum IL-6 levels were decreased compared to control group (P < 0.05). Conclusion: As a result, in this study, we determined that HP and quercetin may play an effective role in regulating insulin metabolism metabolism in diabetes. However, considering the incompatibility of various results in the literature as well as our own results, we think that the actual role of cytokines in the pathogenesis of diabetes is one of the issues that need to be clarified in further studies. Abbreviations used: DM: Diabetes mellitus, MDA: Malondialdehyde, GSH: Glutathione; IL-6: Interleukin-6, TNF-α: Tumor necrosis factor alpha, HP: Hesperidin, Q; Quercetin, STZ: Streptozotocin, TC: Total cholesterol, TG: Triglyceride, HDL-C: High density lipoprotein cholesterol, LDL-C: Low density lipoprotein cholesterol, VLDL-C: Very-low-density lipoprotein cholesterol.

Ninety-six 28-week-old Lohmann White laying hens were utilized to test the antioxidant effects of flavonoids (hesperidin, naringin, and quercetin at 0.5 g/kg diet) during an 8-wk experimental period. At the end of the experiment blood samples were collected to determine total protein, cholesterol, and malondialdehyde (MDA) serum levels as well as activities of glutathione reductase (GR), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and superoxide dismutase (SOD) and level of glutathione (GSH) in erythrocyte lysates. Data were analyzed using one-way ANOVA. Naringin supplementation did not alter serum cholesterol concentration, whereas hesperidin and quercetin supplementations decreased serum cholesterol concentration. Naringin and quercetin supplementations did not affect serum protein concentration. All flavonoids decreased MDA concentration as well as increased GSH-Px, GR, GST, and SOD activities and GSH level, being quercetion superior to hesperidin and naringin. In conclusion, flavonoids, especially quercetin, exert antioxidant activity, which may help improve wellbeing when laying hens are exposed to stressors.

1. The aim of this experiment was to compare the effects of dietary supplementation of hesperidin, naringin and quercetin on laying hen performance, egg quality and egg yolk lipid and protein profiles. 2. A total of 96 Lohmann White laying hens weighing an average of 1500 g at 28 weeks of age were randomly assigned to a basal diet and the basal diet supplemented (0.5 g/kg) with either hesperidin, naringin or quercetin. Each treatment was replicated in 6 cages in an 8-week experimental period. Data were analysed using one-way analysis of variance. 3. None of the dietary flavonoids affected laying performance and eggshell quality. Hesperidin and quercetin supplementations decreased albumen and yolk indexes. 4. As compared to the control group, egg yolk cholesterol content decreased and egg yolk protein content increased in response to dietary hesperidin and quercetin supplementation. The mean egg yolk cholesterol (mg/g) and protein (g/100 g) contents were 10.08/14.28, 16.12/14.08, 14.75/15.04 and 15.15/14.85 for the control group and groups supplemented with naringin, hesperidin and quercetin, respectively. 5. Egg yolk lipid and protein profiles were variable. 6. In conclusion, dietary supplementation of hesperidin or quercetin could be used in the diets during the early laying period to reduce egg yolk cholesterol and increase egg yolk protein, which may be attractive to consumers.

Objective Non-alcoholic fatty liver disease, steatohepatitis and nephropathy are considered among the most important complications of diabetes mellitus (DM), which recently increased due to increased frequency of DM and the prolonged life span of diabetic patients The aim of the present study was to reveal the possible effect of hesperidin (HP) on alpha-klotho (α-KL)/ fibroblast growth factor-23 (FGF-23) pathway in rats with diabetes induced by streptozotocin (STZ). Materials and methods Thirty six male Sprague-Dawley rats were randomly divided into three groups. The rats of the control, diabetes, and treatment groups were fed with standard feed and water throughout the 2-week study. In order to induce diabetes mellitus in rats, those in the diabetes group were administered a single dose of 50 mg/kg STZ. For the DM + HP group, a single dose of 50 mg/kg STZ, when diabetes was induced, hesperidin was administered orally at a dose of 100 mg/kg by gavage. Results The α-KL levels of our study groups, both the liver and kidney α-KL levels and serum α-KL of the STZ-induced diabetic group were statistically significantly lower than the control group (respectively, p < 0.05, p < 0.001, p < 0.05). It was observed that hesperidin administration statistically significantly increased α-KL levels in serum, liver and renal tissue (p < 0.001). Liver, kidney and serum FGF-23 levels of the diabetic group increased significantly in comparison to the control group (respectively, p < 0.05, p < 0.01, p < 0.001). FGF-23 levels that increased in kidney tissue and serum samples of the diabetic group decreased statistically significantly with hesperidin administration (respectively, p < 0.01, p < 0.001). Conclusion The α-KL/FGF-23 pathway is a promising bio-indicator in various cases of systemic toxicity and pathology. In addition, the strong positive effects of hesperidin administration on diabetic toxicity in the liver and kidneys suggest that it may be included in the alternative treatment methods in the future.