SeMet attenuates zearalenone-induced oxidative stress and mitochondrial autophagy in rabbit kidney through activation of Nrf2/Keap1 signaling pathway.

Zearalenone (ZEA) is a secondary metabolite produced by Fusarium oxysporum with strong carcinogenicity, nephrotoxicity and immunotoxicity, etc. It is widely found in moldy cereal grains and their products, which poses a serious health hazard to humans and animals. Selenomethionine (SeMet) is the main form of selenium obtained by animals from plant-based feed ingredients, and has a variety of biological functions including antioxidant, anti-inflammatory, and antiviral. However, the mechanism of protective effect of SeMet against ZEA-induced kidney injury in rabbits is not clear. To explore this issue, we randomly divided fifty 90-day-old Ira rabbits into control (CON), ZEA, low-dose SeMet (L-Se), medium-dose SeMet (M-Se), and high-dose SeMet (H-Se) groups. The SeMet treatment groups were fed diets supplemented with 0.2 mg/kg, 0.35 mg/kg and 0.5 mg/kg SeMet, respectively, for a 21-d experimental period, and on the 15th d of the experiment, rabbits in the ZEA, L-Se, M-Se, and H-Se groups were gavaged with 1.2 mg/kg bw ZEA, and rabbits in the CON group were gavaged with 0.5 mL of olive oil for 7 d consecutively. Serum was collected for biochemical indexes, HE staining was used to observe the morphological changes in the kidney tissues of rabbits, and ELISA was used to detect the content of oxidative stress and inflammatory factor-related indexes in the kidney tissues. Immunohistochemistry, immunofluorescence staining and Western blot were used to detect the expression of relevant proteins in kidney tissues. The results showed that ZEA caused structural damage to the kidney, induced kidney fibrosis, inhibited antioxidant enzyme activity and the Nrf2/Keap1 antioxidant pathway to induce oxidative damage, and activated mitochondrial autophagy. SeMet pretreatment significantly attenuated ZEA-induced kidney injury, oxidative stress and mitochondrial autophagy. Thus, we demonstrate that SeMet alleviates ZEA-induced nephrotoxicity by activating the Nrf2/Keap1 antioxidant pathway. In addition, the protective effect of 0.35 mg/kg SeMet was more significant in this study.