Studies On The Antagonistic Effect Of Selenium On Cadmium-induced Apoptosis And Autophagy Via Regulating PPAR-?/PI3K/Akt Pathway In Chicken Pancreas

Cadmium(Cd)is a heavy metal element,which can be accumulated in various organs and tissues and exert its bio-toxicity via oxidative stress,autophagy and apoptosis.PPAR-?/PI3K/Akt pathway has been found to be involved in lots of physiological and pathological processes,and may relate to heavy metal toxicity.Selenium(Se),an essential trace element,features oxidation resistance and antagonism of heavy metals.Previous studies indicated that Cd has adverse effects on the physiological function and cellular structure of the pancreas,but the concrete toxicity mechanism is still unclear.To explore the role of PPAR-?/PI3K/Akt pathway in Cd-induced apoptosis and autophagy in chicken pancreas and the antagonism mechanism of Se on Cd,128 one-day-old brown laying hens were randomly divided into four groups: control group(with a Se content of 0.2 mg/kg);Se group(with a Se content of 2 mg/kg);Cd group(with a Se content of 0.2 mg/kg;with a Cd content of 150 mg/kg);Se + Cd group(with a Se content of 2 mg/kg;with a Cd content of 150 mg/kg).After 90 days of feeding,the serum of chicken was taken to detect the pancreatic endocrine function by pancreatic endocrine function test kits,and the pancreas was taken to detect the contents of trace elements and toxic elements,ultrastructure,apoptosis status,oxidation status,and expression levels of PPAR-?/PI3K/Akt pathway,apoptosis and autophagy-related genes,respectively.The results are as follows:(1)Results of ion concentration detection showed that compared with control group,Cd concentration in chicken pancreas of Cd group and Se + Cd group were increased by 865.4 and 632.4 times,respectively.Cd treatment decreased the concentration of Se,Cr,Cu,Zn and As,and increased that of Fe,Cd,Al,Ti and Pb in chicken pancreas(P < 0.05).Se supplementation significantly alleviated the changes of Se,Cr,Cu,Zn,Fe,Al,Ti and Pb concentration induced by Cd,and aggravated Li and Co accumulation in chicken pancreas(P < 0.05).Results indicated that Cd could change element profiles and Se could reduce Cd accumulation in pancreas,and the antagonism of Se on Cd may involve various elements profiles in chicken pancreas.(2)The activity of amylase,protease and lipase was significantly lower in Cd group than control group(P < 0.05),and activities of those three enzymes in Se + Cd group were higher than Cd group(P < 0.05)but is still lower than control group(P < 0.05),suggesting that Cd exposure could induce pancreas endocrine function disorder in chicken,but Se supplementation could restore pancreas function to some extent.(3)The nuclei of pancreatic cells were clear and the organelles structure was intact in control group and Se group.Pancreatic cells in Cd group displayed autophagosomes,mitochondrial vacuolation and chromatin agglutination.Ultrastructure damage of pancreas in Se + Cd group was obviously lighter than Cd group.Besides,there were more apoptotic cells in Cd + Se group than in control group,but there were less apoptotic cells in in Cd + Se group than that in the Cd group(P < 0.05).These results indicated Cd exposure induced autophagy and apoptosis of pancreatic cells,and Se supplementation alleviated these damage caused by Cd.(4)The activities of antioxidant enzymes,T-SOD,CAT,GHS-Px and T-AOC,in pancreas were significantly lower(P < 0.05),and the content of MDA,NO and H2O2 and the activity and expression level of i NOS were significantly higher in pancreas of Cd group than control group(P < 0.05).Se supplementation alleviated oxidative stress triggered by Cd(P < 0.05),but it's still not reach the control level(P < 0.05).The results suggested that Cd exposure could induce oxidative stress in chicken pancreas,and Se supplementation could play a role in mitigation.(5)Cd treatment inhibited the expression of PAR-?/PI3K/AKT pathway-related gene PPAR-?,PI3 K and Akt,promoted that of pro-apoptotic gene Bax,Cyt C and caspase 3 and autophagy-related gene LC3-I,LC3-II,Atg 5,dynein and Beclin 1,and inhibited that of m TOR(P < 0.05).The co-treatment of Se can effectively alleviate these changes of gene expressions induced by Cd.The above results showed that Cd induced apoptosis and autophagy of chicken pancreatic cells through inhibiting PPAR-?/PI3K/Akt pathway,and Se could restore the expression of these genes to some extent,thus alleviating the toxic effect of Cd.In conclusion,pancreas is one of the target organs for Cd accumulation.Adverse effects of Cd on pancreas may be involved in many ion profiles of trace elements and toxic element in pancreas.Cd can trigger oxidative stress and the inhibition of PPAR-?/PI3K/AKT pathway-related gene expression,and then induce apoptosis and autophagy,causing pancreatic endocrine dysfunction in chicken.However,Se supplementation can alleviate those changes and antagonize the toxic effect of Cd on the pancreas of chicken.