Molybdenum and Cadmium Combined Exposure Mediates Oxidative Stress and Ferroptosis Induced Kidney Damage in Sheep
The aim of this study was to investigate the role of oxidative stress and ferroptosis in renal tissue injury caused by molybdenum,cadmium and their combined exposure in sheep.Twenty-four sheep aged 2 months were randomly divided into 4 groups,namely control group(Control),molybdenum group(Mo),cadmium group(Cd)and molybdenum cadmium combined group(Mo+Cd).The control group was given equal volume of distilled water,the Mo group was given 45 mg Mo·kg-1BW,group Cd was given 1 mg Cd·kg-1BW,and group Mo+Cd was given 1 mg Cd+45 mg Mo·kg-1 BW.The experimental period lasted for 75 d.At the end of the experiment,serum and kidney tissue were collected,pathological and ultrapathological changes of sheep kidney were observed,and the levels of serum renal function indexes,renal tissue oxida-tive stress and ferroptosis related factors were detected.The results showed that molybdenum,cadmium and their combined exposure increased the levels of serum renal function indicators(cre-atinine,urea and uric acid).In the Mo,Cd,and Mo+Cd groups,the renal tubular epithelial cells underwent degeneration,manifesting as swelling,structural blurring,and lysis.The cyto-plasm contained minute red granules and vacuoles,indicating granular degeneration,vacuolar de-generation,and necrosis.Additionally,the renal tubular lumens were observed to contain pink-stained filamentous components,while the number of red blood cells was elevated in some glo-meruli and interstitial spaces.The results of transmission electron microscopy showed that mo-lybdenum,cadmium and their combined exposure resulted in the reduction of mitochondrial vol-ume,blurring of ridge and vacuolation in renal tubular epithelial cells.The contents of oxidative damage related factors(H2O2,MDA)and Fe ions,the mRNA expression levels of ferroptosis related factors(NCOA4,ACSL4,TFR1 and PTGS2)and the protein expression levels of PTGS2 were increased in Mo and Cd groups.The mRNA and protein expression levels of antioxi-dant related factors(GSH,CAT and GSH-Px)and ferroptosis related factors(SLC7A11,GPX4 and FTH1)were decreased,and the above changes were more obvious in Mo+Cd group.Pear-son correlation analysis showed that the levels of oxidative damage related factors(H2O2,MDA)and Fe ions were positively correlated with the expression levels of ferroptosis related factors(NCOA4,ACSL4,TFR1 and PTGS2),and negatively correlated with the expression levels of ferroptosis related factors(SLC7A11,GPX4 and FTH1).The correlation of antioxidant related factors(GSH,CAT and GSH-Px)and ferroptosis related factors was opposite to that of oxida-tive damage related factors.This study shows that molybdenum cadmium and its combined expo-sure induced renal oxidative stress and ferroptosis in sheep,resulting in renal tissue damage,and molybdenum,cadmium toxicity has a synergistic effect.
万方数据
维普
