Selenium Alleviates Cadmium-induced The Expression Of Cell Aging Related Factors Via Mitochondrial Quality Control In The Livers Of Sheep

To investigate the effects of cadmium on senescence of sheep hepatocytes and the antagonistic effects of selenium on cadmium toxicity.Forty-eight sheep were randomly divided into 4 groups:control group,selenium group(0.34 mg Se·kg^-1·BW),cadmium group(1 mg Cd·kg^-1·BW),and selenium+cadmium group(0.34 mg Se·kg^-1·BW+1mg Cd·kg^-1·BW).The experimental group was given corresponding doses of selenium and cadmium solutions every day,and the control group was given the same amount of normal saline.The experimental period was 50 d.The quality and functions of mitochondria and the aging level of hepatocytes in sheep livers were evaluated by tissue section observation,transmission electron microscope observation,antioxidant index determination,immunohistochemical observation,immunofluorescence co-localization observation,real-time fluorescence quantitative determination and western blotting.The results are as follows:1.Selenium could alleviate cadmium-induced hepatocyte granular degeneration and vacuolar degeneration,mitochondrial vacuolization,the down-regulation of mitochondrial T-SOD,CAT enzyme activity and GSH,ATP content level,and the up-regulation of H₂O₂ and MDA content level.2.Selenium alleviated the down-regulation of mitochondrial biosynthesis-related genes（FOXO1,FOXO3,SIRT1,SIRT3 and PGC-1α）mRNA expression and PGC-1αand SIRT1 protein expression induced by cadmium in sheep livers.3.Selenium alleviated the down-regulation of mitochondrial fusion-related genes（Mfn1,Mfn2 and OPA1）mRNA expression and Mfn2 and OPA1 protein expression induced by cadmium in sheep livers.4.Selenium alleviated cadmium-induced the up-regulation of mitochondrial fission-related genes（Drp1,MFF and Fis1）mRNA expression and protein expression in sheep liver.5.Selenium delayed cadmium-induced up-regulation of mitophagy-related genes（PINK1,Parkin,P62,LC3A and LC3B）mRNA expression and PINK1,Parkin and LC3B protein expression in sheep liver.In addition,selenium could reduce the increase in the number of colocalization puncta of LC3B/COX IV and Parkin/COX IV induced by cadmium in sheep liver.6.Selenium alleviated cadmium-induced the up-regulation of aging-related secretory phenotype factors（IL6,CCL8 and HGF）,GLB1 and P21 mRNA expression levels and IL6 and P21 protein expression levels,the down-regulation of MCM2 mRNA expression level,and P21 nuclear accumulation in sheep liver.In summary,selenium might alleviate cadmium-mediated senescence in sheep hepatocytes by regulating mitochondrial biosynthesis,mitochondrial fission,mitochondrial fusion and mitophagy（mitochondrial quality control）.