Selenium Alleviates Cadmium-induced Lungs Damage Via FUNDC1-mediated Mitochondrial Quality Control System In The Sheep

Cadmium is a poisonous metal element that causes mitochondrial dysfunction.Selenium can reduce the damage of Cd to various organs of animals,but the protective mechanism of Se in Cd-induced lung injury has not been fully elucidated.To investigate the protective effect of selenium on lung injury induced by cadmium and its mechanism,and to provide a theoretical basis for selenium as a potential feed or food additive.48sheep were divided into 4 groups,control group,cadmium group（1 mg/kg body weight of cadmium）,selenium group（0.34 mg/kg body weight of selenium）,and cadmium+selenium group（0.34 mg/kg body weight of selenium+1 mg/kg body weight of cadmium）administered intragastrically for 50 days.Hematoxylin-eosin staining,transmission electron microscopy,immunofluorescence,real-time fluorescence quantification and protein immunoblotting were used to detect antioxidant indexes,mitochondrial morphology and function,mitochondrial biogenesis,mitochondrial dynamics,mitophagy and other related indexes to assess lung injury caused by cadmium exposure and the protective effect of selenium.The test results are as follows:1,Cadmium caused inflammatory cell infiltration and alveolar wall thickening,and also promoted mitochondrial vacuolization and autophagic vesicle formation in lung tissue.2,Cadmium treatment decreased the contents of ATP and GSH and the activities of CAT and T-SOD in sheep lung tissue,while increasing the contents of MDA and H₂O₂in lung tissue.3,Cadmium treatment down-regulated the expression levels of mitochondrial biogenesis and mitochondrial fusion,but up-regulated the expression levels of mitochondrial fission and mitophagy mediated by FUNDC1,and the intensity of immunofluorescence co-localization sites of LC3B/COX IV and LC3B/FUNDC1 was increased after cadmium treatment.4,Selenium could alleviate cadmium-induced damage to alveolar wall cell morphology and structure,improve the antioxidant capacity as well as mitochondrial biosynthesis and fusion capacity of lung tissue,and inhibit mitochondrial fission and mitophagy in lung.In conclusion,selenium can alleviate cadmium-induced lung injury in sheep through FUNDC1-mediated mitochondrial quality control pathway.