Effect Of Molybdenum And Cadmium Co-exposure On Hepatocyte Damage In Ducks

To explore the impacts of Cd and Mo co-exposure on pyroptosis and apoptosis by PTEN/PI3K/AKT pathway in the liver of ducks,160 healthy 8-day-old Shaoxing ducks（half male and female）were randomly assigned to 4 groups:Control group（Control group,0 mg/kg Mo and 0 mg/kg Cd）,Mo group（Mo group,100 mg/kg Mo）,Cd group（Cd group,4 mg/kg Cd）,and Mo+Cd group（Mo+Cd group,100 mg/kg Mo and 4 mg/kg Cd）,the sources of Cd and Mo were Cd sulfate（3Cd SO₄·8H₂O）and hexaammonium molybdate[（NH₄）₆Mo₇O₂₄·4H₂O],respectively.At the 16th week of the experiment,10 ducks in each group were randomly selected,the body weight of ducks was measured,blood and livers were collected.whole liver weight and liver index,liver histopathology and ultrastructure,trace element content,liver function and expression of PTEN/PI3K/AKT pathway,apoptosis and pyroptosis related factors in liver were assayed.The results were as follows:1.Mo or/and Cd led to a significant increase in liver index,hepatocytes swelling,fatty degeneration of liver cells and inflammatory cells around blood vessels,hepatic sinusoidal space narrowing,hepatic cord disorder;mitochondrial swelling,disruption of cristae membrane and even vacuolization,nucleus deformation and karyopyknosis,AST,TBILI,DBILI,ALP and ALT levels were visibly increased and ALB and TP levels were remarkably decreased,and the Mo-Cd combined group and the single group had a very significant difference.2.Mo or/and Cd could obviously increase the contents of Cd,Mo,Ag and Pb,and evidently reduce the contents of Cu,Fe,Zn,Se,As and Ni,and the Mo-Cd combined group and the single group had a very significant difference.3.Mo or/and Cd can significantly up-regulate Bak-1,Bax,Cyt C,Caspase-3 mRNA levels and Cleaved-Caspase-3/Caspase-3 protein levels,and remarkably down-regulate Bcl-2 mRNA levels and Bcl-2/Bax ratio,and the Mo-Cd combined group and the single group had a very significant difference.4.Mo or/and Cd could obviously increase Caspase-1,NLRP3,NEK7,ASC,GSDME,GSDMA,IL-1β,IL-18 mRNA expression levels and Caspase-1 p20,NLRP3,ASC,GSDMD protein levels and IL-1βand IL-18 contents,and the Mo-Cd combined group and the single group had a very significant difference.5.Mo or/and Cd could remarkably up-regulate the expression levels of PTEN mRNA and protein,and reduce the levels of PI3K,AKT mRNA and PI3K,p-AKT/AKT protein,and the Mo-Cd combined group and the single group had a very significant difference.Conclusion:Mo or/and cadmium lead to duck liver index,liver tissue morphology and liver function abnormalities,imbalance of trace elements,activation of PTEN/PI3K/AKT pathway and induction of hepatocyte apoptosis and pyroptosis in duck liver.Therefore,Mo or/and Cd-induced hepatocyte apoptosis and pyroptosis in duck liver cells may be related to the activation of PTEN/PI3K/AKT pathway,Mo and Cd association aggravates the toxicity of duck liver...