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

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.

Se Alleviated Oxidative Stress-Mediated Complex Poisoning Mechanism in Pb-Treated Chicken Kidneys: Inflammation, Heat Shock Response, and Autophagy

“…Pb promoted protein levels of Beclin1, LC3-I, and LC3-II; and induced autophagy in rat hippocampi [54]. Han et al (2017) reported that Pb increased mRNA and protein levels of ATG5, Beclin-1, Dynein, LC3-I, and LC3-II; decreased mRNA and protein levels of mTOR; and induced autophagy in chicken spleens [12]. Our present research is consistent with above studies.…”

“…[49] and hearts [50] of chickens. Se was reported by one of the articles to alleviate spleen toxicity in a chicken model induced by Pb via the modulation of oxidative stress, in ammation, and autophagy [12]. Se alleviated protein increase of ATG5, Beclin1, Dynein, LC3-I, and LC3-II and protein decrease of mTOR in Cd-induced chicken pancreas [58].…”

“…Pb induced oxidative stress which led to autophagy in the spleens of chickens [12] and mice [13]. Ge et al (2018) reported that autophagy was intertwined with in ammation, and cytokines can help mediate this interaction [14].…”

N‐acetylcysteine alleviated paraquat‐induced mitochondrial fragmentation and autophagy in primary murine neural progenitor cells

“…Of note, other studies indicate that oxidative stress is closely associated with autophagy. Oxidative stress may inhibit mTOR activity and promote autophagy in the spleen of the chicken (Han et al, ). In our current study, we observed the ultrastructure of the mNPCs by TEM.…”

Mitochondrion: a sensitive target for Pb exposure

“…Studies have indicated that Pb exposure could significantly inhibit the antioxidant system in mitochondria. The activities of GPX, SOD, CAT, GSH are obviously decreased while the activity of iNOS is opposite (Chi et al, 2017;Han et al, 2017;Pal et al, 2013). In addition, the oxygen is rapidly consumed due to the oxidation of the polyunsaturated fatty acid acyl chain via ROS.…”