Selenium deficiency increased duodenal permeability and decreased expression of antimicrobial peptides by activating ROS/NF-κB signal pathway in chickens.

Selenium (Se) is an essential trace element for the body. Various organs of the body, including the intestine, are affected by its deficiency. Se deficiency can induce oxidative stress and inflammatory responses in the intestine. It can also increase intestinal permeability and decrease intestinal immune function in mammals. However, the detailed studies, conducted on the intestinal molecular mechanisms of Se deficiency-induced injury in poultry, are limited. This study explored the adverse effects of Se deficiency on intestinal permeability and its mechanism. A Se-deficient chicken model was established, and the morphological changes in the chicken duodenum tissues were observed using a light microscope and transmission electron microscope (TEM). Western blotting, qRT-PCR, and other methods were used to detect the expression levels of selenoproteins, oxidative stress indicators, inflammatory factors, tight junction (TJ) proteins, antimicrobial peptides, and other related indicators in intestinal tissues. The results showed that Se deficiency could decrease the expression levels of selenoproteins and antioxidant capacity, activate the nuclear factor kappa-B (NF-κB) pathway, cause inflammation, and decrease the expression levels of TJ proteins and antimicrobial peptides in the duodenum tissues. The study also demonstrated that Se deficiency could increase intestinal permeability and decrease antimicrobial peptides via reactive oxygen species (ROS)/NF-κB. This study provided a theoretical basis for the scientific prevention and control of Se deficiency in poultry. Se deficiency decreased the expression levels of selenoproteins and increased ROS levels to activate the NF-κB pathway, resulting in the production of pro-inflammatory cytokines, reducing the expression levels of TJ protein, and weakening the expression of antimicrobial peptides, which contributed to the higher intestinal permeability. Oxidative stress weakened the expression of antimicrobial peptides.

Cadmium induces the thymus apoptosis of pigs through ROS-dependent PTEN/PI3K/AKT signaling pathway.

Cadmium (Cd) is a transition metal that is toxic to living organisms in the environment and endangers living organisms. To explore whether Cd induces apoptosis in pig thymus and its possible mechanism, the role Cd induction of the PTEN/PI3K/Akt pathway in apoptosis of thymus cells was studied in pigs. We found that Cd exposure (the feed is treated with Cd) significantly increased Cd accumulation in the thymus of pigs. The TUNEL assay confirmed the typical apoptotic characteristics of thymus in Cd group. Moreover, in the Cd group, the activities of antioxidant indices decreased significantly, while the levels of oxidative stress indexes increased significantly, and the mRNA levels of GSH, CAT, Gpx1, GST, SOD1, and SOD2 decreased obviously. Moreover, the mRNA and protein levels of PTEN/PI3K/AKT and apoptosis-related genes were detected by qPCR and western blotting. The results show that the expressions of PI3K and AKT decreased, while the expression of PTEN increased, indicating that pathway activated. With the PTEN/PI3K/AKT pathway regulating, Bcl-2 expression decreased. Conversely, the mRNA and protein expression of apoptosis-related genes were up-regulated. In conclusion, accumulation of Cd in the pigs caused oxidative damage to immune tissues. In addition, Cd-induced oxidative stress activates the PTEN/PI3K/AKT pathway, inducing apoptosis in the thymus of pigs.

Cadmium induces apoptosis of pig lymph nodes by regulating the PI3K/AKT/HIF-1α pathway.

OBJECTIVE: This study was aimed to explore the possible mechanism of environmental metal cadmium (Cd) inducing apoptosis of pig lymph nodes. METHOD: 10 healthy 6-week-old weaned piglets were randomly divided into two groups (n = 5 pigs/group). The control group was fed with a basic diet, and the test group was fed with a basic diet of 20 mg/kg CdCl2. RESULTS: The Cd deposition in mesenteric lymph nodes (MLN), inguinal lymph nodes (ILN) and submaxillary lymph nodes (SLN) after Cd exposure was 2.37 folds, 1.4 folds and 1.8 folds of the control group, respectively. And the rate of MLN and ILN apoptotic cells in the Cd group was 4.11 folds and 9.18 folds of the control group, respectively. The mRNA levels of SOD1, SOD2, CAT, GPX1 and GSH in the Cd group were reduced. Similarly, the two-phase detoxification enzymes had a significant downward trend. Cd exposure decreased the activities of GSH, GSH-Px, SOD, CAT, and increased H2O2 and MDA levels. The mRNA and protein levels of Drp1 and Mff in the Cd group were higher than the corresponding control group, and the mRNA and protein levels of Mfn1 and Mfn2 were lower than those in the control group. In addition, the mRNA and protein levels of pro-apoptotic genes in the Cd group were lower than those in the control group. Cd can significantly reduce the expression of PI3K, AKT and HIF-1α in the three lymph nodes. In summary, Cd induces oxidative stress and regulates the PI3K/AKT/HIF-1α signal transduction pathway to cause mitochondrial dynamics disorder, which leads to the apoptosis of pig lymph nodes, suggesting that Cd-induced mitochondrial pathway apoptosis is related to Cd pig lymph nodes play an important role in the toxicity mechanism.

MicroRNA-223 triggers inflammation in porcine aorta by activating NLRP3 inflammasome under selenium deficiency.

Selenium (Se) is an essential trace element in organism. Se deficiency can cause many diseases, including vascular disease. Studies have shown that inflammation is the main inducement of vascular disease, microRNA (miRNA) can influence inflammation in various ways, and Se deficiency can affect miRNAs expression. To study the mechanism of aorta damage caused by Se deficiency, we constructed a Se deficiency porcine aorta model and found that Se deficiency can significantly inhibit miR-223, which downregulates the expression of nucleotide-binding oligomerization domain-like receptor family 3 (NLRP3). Subsequently, we found that in Se deficiency group, NLRP3, and its downstream (caspase-1, apoptosis-related spot-like protein [ASC], IL-18, IL-1ß) expression was significantly increased. In vitro, we cultured pig iliac endothelium cell lines, and constructed miR-223 knockdown and overexpression models. NLRP3 messenger RNA and protein levels were significant increased in the knockdown group, and decreased in the overexpression group. The results of this study show that Se deficiency in porcine arteries can induce inflammation through miR-223/NLRP3.

Astilbin protects chicken peripheral blood lymphocytes from cadmium-induced necroptosis via oxidative stress and the PI3K/Akt pathway.

Astilbin (ASB), a dihydroflavonol glycoside, is widely found in a variety of plants and in functional foods and acts as a powerful antioxidant. The aim of this study was to investigate the underlying mechanisms involved in the antagonistic effects of ASB on cadmium (Cd)-induced necroptosis in chicken peripheral blood lymphocytes. Peripheral blood lymphocytes were aseptically collected from Roman white hens and then randomly divided into five groups: the control group was incubated without additional reagents, while the other groups were incubated with Cd, ASB, a combination of Cd and ASB, and 0.1% DMSO. After a 24 h treatment, cell samples were collected. The results showed that some morphological changes consistent with necroptosis were observed in the Cd-treated groups, suggesting the occurrence of necroptosis. Simultaneously, antioxidant activity markers (CAT, SOD, GSH, GSH-px, and T-AOC) decreased and indicators of oxidative stress (MDA, iNOS, NO, H2O2, ·OH and ROS) increased. The production of ROS induced the activation of the PI3K/Akt signaling pathway, as the expression levels of PI3K, Akt and PDK1 were significantly elevated. Additionally, the expression levels of RIPK3, RIPK1, MLKL, TAK1, TAB2 and TAB3 were increased and that of Caspase-8 was decreased, which could cause the necroptosis. However, the most important our results was that ASB supplements remarkably attenuated the Cd-induced effects. We conclude that the Cd treatment promoted an imbalance of the antioxidant status and activated the PI3K/Akt pathway, leading to necroptosis in chicken peripheral blood lymphocytes, and that ASB was able to partially ameliorate the effect of Cd-induced necroptosis.