Role Of Selenoprotein GPX4-mediated Ferroptosis And Pyroptosis In Selenium Alleviating Cadmium-induced Kidney Injury In Sheep

To explore the role of selenoprotein GPX4 mediated ferroptosis and pyroptosis in selenium alleviating cadmium induced kidney injury in sheep,48 sheep were randomly divided into four groups:control group,cadmium group(1 mg Cd·kg^-1·BW),cadmium+selenium group(1 mg Cd·kg^-1·BW+0.34 mg Se·Kg^-1·BW),and selenium group(0.34 mg Se·Kg^-1·BW)for 50 days.The levels of renal injury,ferroptosis and pyroptosis in sheep were evaluated by histological observation,transmission electron microscopy,antioxidant index determination,immunohistochemistry,immunofluorescence observation,real-time fluorescence quantitative determination,and protein immunoblotting.The results showed that cadmium could cause cavities in renal tubular epithelial cells and glomerular cell damage in sheep,significantly reduced the levels of GSH,NADPH,CAT,and SOD in kidney tissue（P<0.05）,significantly increased the level of MDA（P<0.01）,increased the expression of NLRP3,GSDMD-N proteins,and the degree of fluorescence co-localization of FTH1/LC3B,as well as the expression of PTGS2,NCOA4,TFR1,LC3B,NLRP3,ASC,Caspase-1,GSDMD,IL-1βand IL-18 were upregulated（P<0.05 or P<0.01）,while the expression of GPX1,GPX4,TXNRD1,SELP,SP1,SLC7A11,SLC4A2,and FTH1 were downregulated（P<0.05 or P<0.01）.However,selenium addition can alleviate the impact of cadmium on these indicators.Therefore,the results showed that selenium could alleviate cadmium induced kidney damage in sheep through ferroptosis and pyroptosis mediated by selenoprotein GPX4.