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.