Hydroxytyrosol affects antioxidant Nrf2 expression in the kidneys of diabetic rats

Abstract

Aim: Diabetic nephropathy is the result of oxidative stress caused by chronic hyperglycemia. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that responds to oxidative stress. Nrf2 relieves oxidative stress, inflammation, and fibrosis associated with diabetes in the kidneys. In this study, we investigated the effects of hydroxytyrosol, which is a polyphenolic compound with proven antioxidant activity, on Nrf2 expression in diabetic kidneys. Methods: Forty male Wistar rats were used in our study and the rats were divided into four groups as control (sterile water only), hydroxytyrosol (HT) (10mg/kg hydroxytyrosol administered intraperitoneally (ip) for 30 days), streptozotocin (STZ) (diabetes was induced by administering a single dose of 55 mg/kg streptozotocin ip), and streptozotocin + hydroxytyrosol (STZ+HT) (single dose of 55 mg/kg streptozotocin and 10 mg/kg hydroxytyrosol administered ip for 30 days). At the end of the study, Nrf2 expression in kidney tissue was evaluated by immunohistochemistry and Western blot. Results: Immunohistochemistry and Western blot findings of Nrf2 were similar. It was found that while Nrf2 expression increased significantly in the HT group compared to the control group, whereas it decreased significantly in the STZ group (p<0.001). In the STZ+HT group, Nrf2 expression was found to be significantly increased compared to the STZ group (p<0.001). Conclusions: It was found that hydroxytyrosol with known antioxidant activity increased Nrf2 expression in diabetic rats. These results suggest that hydroxytyrosol may mitigate diabetic nephropathy by Nrf2-induced reduction in oxidative stress, inflammation, and fibrosis.