Antagonistic effects of selenium on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens.

Yujing Han,Mingjun Su,Zhihui Wang,Dongbo Sun,Ning Jiang,Chunqiu Li

doi:10.18632/oncotarget.16736

Abstract

Lead (Pb) may damage the immune function in human and animal. Selenium (Se) has antagonistic effects on Pb. In our study, brown layer chickens were randomly allocated to control group, Se group (1 mg/kg Se), Se+Pb group (1 mg/kg Se and 350 mg/kg Pb), and Pb group (350 mg/kg Pb). The chickens were sacrificed on the 90th day; spleen tissues were subjected to observation of ultrastructure and detection of spleen-related indexes. The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme GPX, SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin (mTOR) was downregulated. The results of transmission electron microscopy indicated that Pb induced mitochondrial fragmentation, and triggered autophagy in the spleen of chickens. The Se and Pb co-treatment remarkably alleviated these injuries induced by Pb in the spleen of chickens. In conclusion, Pb can induce the oxidative stress to influence the mitochondrial dynamics balance and lead to autophagy, which triggers the immune dysfunction in the spleen of chickens; the Se exhibits the antagonistic effects on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens.

Highlights

Lead (Pb) is a well-known highly toxic element for organisms and has the potential to threaten ecosystem
The results revealed that in the Pb group, expression levels of the cytokines IL-1 and TNF-α significantly increased, and expression levels of IL-2 and INF-γ significantly decreased; activities of antioxidant enzyme glutathione peroxidase (GPX), SOD and CAT significantly decreased, and expression level of malondialdehyde (MDA) significantly increased; expression levels of mitochondrial fission-related genes (Mff and Drp1) significantly increased, and expression levels of mitochondrial fusion-related genes (Opa1, Mfn1 and Mfn2) significantly decreased; expression of autophagy-related genes (Beclin 1, Dynein, Atg 5, LC3-I and LC-II) was upregulated, while expression of mammalian target of rapamycin was downregulated
Pb can induce the oxidative stress to influence the mitochondrial dynamics balance and lead to autophagy, which triggers the immune dysfunction in the spleen of chickens; the Se exhibits the antagonistic effects on lead-induced autophagy by influencing mitochondrial dynamics in the spleen of chickens

Summary

Introduction

Lead (Pb) is a well-known highly toxic element for organisms and has the potential to threaten ecosystem. Excessive exposure to Pb may induce several pathological changes in humans and animals, involving in encephalopathy, convulsion and even death [4,5,6]. Corsetti et al (2016) reported that spleen is one of the target organs of Pb toxicity; excessive exposure to Pb may induce autophagy in the spleen [12]; in fishes, spleen exhibits a high content of Pb and histopathological alterations when treated by Pb [13]. The evidence convinced that mitochondrial fission could promote mitochondrial autophagy in mouse embryonic fibroblasts, human fibroblasts, and cardiac cells [14,15,16]; in adult cardiomyocytes, Drp, a GTPase, regulates mitochondrial fission, and mediates autophagy [17]; the overexpression of the OPA1 decreases mitochondrial autophagy in mice [14]. Accumulating reports indicate that autophagy is one of the most important targets for investigation of mechanisms of Pb toxicity for organism

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