scholarly journals Zearalenone Exposure Triggered Cecal Physical Barrier Injury through the TGF-β1/Smads Signaling Pathway in Weaned Piglets

Toxins ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 902
Pengfei Zhang ◽  
Changwei Jing ◽  
Ming Liang ◽  
Shuzhen Jiang ◽  
Libo Huang ◽  

This study aims to investigate the effects of exposure to different dosages of zearalenone (ZEA) on cecal physical barrier functions and its mechanisms based on the TGF-β1/Smads signaling pathway in weaned piglets. Thirty-two weaned piglets were allotted to four groups and fed a basal diet supplemented with ZEA at 0, 0.15, 1.5, and 3.0 mg/kg, respectively. The results showed that 1.5 and 3.0 mg/kg ZEA damaged cecum morphology and microvilli, and changed distribution and shape of M cells. Moreover, 1.5 and 3.0 mg/kg ZEA decreased numbers of goblet cells, the expressions of TFF3 and tight junction proteins, and inhibited the TGF-β1/Smads signaling pathway. Interestingly, the 0.15 mg/kg ZEA had no significant effect on cecal physical barrier functions but decreased the expressions of Smad3, p-Smad3 and Smad7. Our study suggests that high-dose ZEA exposure impairs cecal physical barrier functions through inhibiting the TGF-β1/Smads signaling pathway, but low-dose ZEA had no significant effect on cecum morphology and integrity through inhibiting the expression of smad7. These findings provide a scientific basis for helping people explore how to reduce the toxicity of ZEA in feeds.

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 663 ◽  
Xi-Chun Wang ◽  
Ya-Fei Zhang ◽  
Li Cao ◽  
Lei Zhu ◽  
Ying-Ying Huang ◽  

Deoxynivalenol (DON) is highly toxic to animals and humans, but pigs are most sensitive to it. The porcine mucosal injury related mechanism of DON is not yet fully clarified. Here, we investigated DON-induced injury in the intestinal tissues of piglet. Thirty weanling piglets [(Duroc × Landrace) × Yorkshire] were randomly divided into three groups according to single factor experimental design (10 piglets each group). Piglets were fed a basal diet in the control group, while low and high dose groups were fed a DON diet (1300 and 2200 μg/kg, respectively) for 60 days. Scanning electron microscopy results indicated that the ultrastructure of intestinal epithelial cells in the DON-treated group was damaged. The distribution and optical density (OD) values of zonula occludens 1 (ZO-1) protein in the intestinal tissues of DON-treated groups were decreased. At higher DON dosage, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α mRNA levels were elevated in the intestinal tissues. The mRNA and protein levels of NF-κB p65, IκB-α, IKKα/β, iNOS, and COX-2 in the small intestinal mucosa were abnormally altered with an increase in DON concentration. These results indicate that DON can persuade intestinal damage and inflammatory responses in piglets via the nuclear factor-κB signaling pathway.

2007 ◽  
Vol 35 (06) ◽  
pp. 995-1009 ◽  
Hsin-Fang Chang ◽  
Yun-Ho Lin ◽  
Chia-Chou Chu ◽  
Shu-Ju Wu ◽  
Ya-Hui Tsai ◽  

This study investigated the effects of the combined extracts of Ginkgo biloba, Panax ginseng, and Schizandra chinensis at different doses on hepatic antioxidant status and fibrosis in rats with carbon tetrachloride ( CCl 4)-induced liver injury. Male Sprague-Dawley rats ( n = 8–12 per group) were divided into the control, CCl 4, CCl 4 + silymarin (0.35%), CCl 4 + low-dose herbal extract (0.24% of Ginkgo biloba, Panax ginseng, and Schizandra chinensis extract at 1:1:1; LE), and CCl 4 + high-dose herbal extract (1.20% of the same herbal extract; HE) groups. Silymarin or herbal extract was orally given to rats a week before chronic intraperitoneal injection with CCl 4 for 6 weeks. The pathological results showed that herbal extract suppressed hepatic bile duct proliferation, and low-dose herbal extract inhibited liver fibrosis. Hepatic superoxide dismutase (SOD) activity was lower in the CCl 4 group, but there was no difference in the silymarin or herbal extract treated groups compared to the control group. Hepatic catalase activity and the ratio of reduced to oxidized glutathione were significantly higher ( p < 0.05) in the HE group than those in the CCl 4 group. Silymarin and herbal extract reversed the impaired hepatic total antioxidant status ( p < 0.05). Herbal extract partially reduced the elevated hepatic lipid peroxides. Hepatic transforming growth factor-β1 (TGF-β1) level decreased significantly ( p < 0.05) in the LE group. Therefore, high-dose herbal extract improved hepatic antioxidant capacity through enhancing catalase activity and glutathione redox status, whereas low-dose herbal extract inhibited liver fibrosis through decreasing hepatic TGF-β1 level in rats with CCl 4-induced liver injury.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14652-e14652
Michael Molyneaux ◽  
John Xu ◽  
David M. Evans ◽  
Patrick Lu

e14652 Background: Cholangiocarcinoma (CCA) is a hepatobiliary cancer and although there have been advances recently there is a need for additional treatment methods for patients. Over expressions of TGF-β1 and COX-2 have been reported to play key roles in tumorigenesis of CCA. We studied the effect of STP705 on the growth of HuCCT-1 xenograft tumors in nude mice. STP705 is a TGF-β1/COX-2 specific siRNA combination product formulated in Histidine-Lysine co-Polymer nanoparticle delivery system. Methods: HuCCT-1 xenograft tumors were implanted subcutaneously into 24 BALB/c nude female mice (n = 8/group). Group 1 received vehicle control, group 2 (low-dose) received 8µg of STP705, and group 3 (high-dose) received 16µg of STP705. Intratumoral test article administration and tumor volume measurements were conducted twice a week for 3-weeks. Qualitative analysis was performed on H&E, Picrosirius red (PSR) and immunohistochemistry (IHC) stained sections of tumor tissues. Results: High- and low- dose groups of STP705 reported significantly lower mean tumor volume at day 21 (p = 0.005 & p = 0.036, respectively) as compared to control group. High-dose group reported significantly lower tumor volume at days 11 (p = 0.042), 15 (p = 0.003), and 18 (p = 0.007) as compared to the control group. IHC assessment demonstrated that STP705-treated animals had significantly lower (H-score ± SEM) TGF-β1, COX-2, HSP70, Bcl-xL and MMP-9 staining (52±9, 39±4, 178±8, 25±7 & 7±1, respectively) as compared to control animals (94±11, 66±8, 213±7, 59±8 & 11±2, respectively – with p < 0.05). Assessment of Caspase-3 and H&E (necrosis and inflammation) slides reported higher mean score for STP705-treated animals, while PSR staining reported lower fibroplasia for STP705-treated animals as compared to the control animals. Conclusions: The data suggests that STP705-treatment suppresses TGF-β1 and COX-2 expression resulting in inhibition of (i) tumor cell survival, (ii) fibrosis, (iii) promotes apoptosis, and (iv)decreased invasiveness of tumor cells. Overall, STP705 is an innovative siRNA-based treatment that results in significant suppression of tumor growth in a HuCCT-1 xenograft mouse tumor model.

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1144
Yongwei Zhao ◽  
Yu Niu ◽  
Jintian He ◽  
Lili Zhang ◽  
Chao Wang ◽  

The object of present study was to evaluate the effects of dihydroartemisinin (DHA) supplementation on the hepatic antioxidant capacity in IUGR-affected weaned piglets. Eight piglets with normal birth weight (NBW) and sixteen IUGR-affected piglets were selected. Piglets were weaned at 21 days. NBW and IUGR groups were fed a basal diet and the ID group was fed the basal diet supplemented with 80 mg/kg DHA for 28 days. The result indicated that compared with NBW piglets, IUGR-affected piglets increased (p < 0.05) the concentration of malondialdehyde (MDA) and decreased (p < 0.05) the serum activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In addition, IUGR-affected piglets showed increased (p < 0.05) hepatic concentrations of protein carbonyl (PC), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and oxidized glutathione (GSSG), and an increased GSSG:GSH value. IUGR-affected piglets exhibited lower (p < 0.05) activities of GSH-Px, T-SOD, total antioxidant capacity (T-AOC), and the concentration of glutathione (GSH). DHA supplementation decreased (p < 0.05) the serum concentration of MDA and increased the serum activities of T-AOC, T-SOD, GSH-Px, and CAT. The ID group showed decreased (p < 0.05) concentrations of MDA, PC, 8-OHdG, and GSSG, and a decreased GSSG:GSH value in the liver. The hepatic activity of T-SOD and the concentration of GSH were increased (p < 0.05) in the liver of ID group. IUGR-affected piglets downregulated (p < 0.05) mRNA expression of nuclear erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and CAT. DHA supplementation increased (p < 0.05) mRNA expression of Nrf2, HO-1, GPx1, and CAT in the ID group. In addition, the protein expression of Nrf2 was downregulated (p < 0.05) in the liver of IUGR-affected piglets and DHA supplementation increased (p < 0.05) the protein content of Nrf2 and HO-1. In conclusion, DHA may be beneficial in alleviating oxidative damage induced by IUGR through the Nrf2/ARE signaling pathway in the liver.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 470-471
Min Song ◽  
Yijie Fan ◽  
Han Su ◽  
Fenglin Zhang ◽  
Fangfang Liu ◽  

Abstract This study aimed to investigate the effects of ActigenTM, a second-generation mannan rich fraction, on growth performance, intestinal barrier functions and inflammation in weaned piglets. A total of 150 weaned piglets were randomly assigned to Control, antibiotics and Actigen groups and received 1 of 3 dietary treatments: a basal antibiotics-free diet to which 100 mg/kg antibiotics or 800 mg/kg Actigen were added. Body weight and feed intake were recorded. On day 28, 10 piglets per treatment were selected to collect blood, small intestinal segments and mucosa samples. Intestinal morphology and goblet cell number were determined. Expression of tight junction proteins and Toll Like receptor 4 (TLR4) signaling were detected. D-lactic acid (DLA) and inflammatory cytokines in serum were also measured. Actigen or antibiotics supplemented diets significantly reduced incidence of diarrhea, with no effect on growth performance. Intestinal morphology revealed that antibiotics significantly decreased, while Actigen markedly increased the villus height and the ratio of villus height to crypt depth. PAS staining demonstrated that the goblet cell number was markedly elevated in jejunum of the Actigen fed piglets. In addition, the expression of tight junction proteins was significantly decreased and increased by antibiotics and Actigen use, respectively. Accordingly, the intestinal permeability was elevated by antibiotics use, with the increased serum DLA. Furthermore, Actigen fed piglets had lower serum proinflammatory cytokine TNF-α and higher serum anti-inflammatory cytokine IL-10. In contrast, antibiotics use led to the increase of serum IL-1β. Moreover, the expression of TLR4, Myd88, and IKKβ phosphyorlation were enhanced by antibiotics use, suggesting the activation of TLR4 signaling pathway. However, Actigen supplemented diet had no effect on the TLR4 signaling pathway. In conclusion, compared with the control and antibiotics groups, Actigen supplemented diet had the similar or improved effects on growth performance, intestinal barrier functions and inflammation in weaned piglets.

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6060 ◽  
Shiqiong Wang ◽  
Haihua Li ◽  
Chenhong Du ◽  
Qian Liu ◽  
Dongji Yang ◽  

Lactobacillus supplementation is beneficial to the barrier function of the intestinal physical barrier in piglets. However, the mechanisms underlying this beneficial function remain largely unknown. Here, we investigated the effects of dietary supplementation with Lactobacillus acidophilus on the performance, intestinal physical barrier functioning, and NOD-like receptors (NLRs) expression in weaned piglets. Sixteen weaned piglets were randomly allocated to two groups. The control group received a corn-soybean basal diet, while the treatment group received the same diet adding 0.1% L. acidophilus, for 14 days. As a result, dietary L. acidophilus supplementation was found to increase the average daily gain (ADG) (P < 0.05), reduced serum diamine oxidase (DAO) activity (P < 0.05), increased the mRNA expression and protein abundance of occludin in the jejunum and ileum (P < 0.01), reduced the mRNA levels of NOD1 (P < 0.01), receptor interacting serine/threonine kinase 2 (RIPK2) (P < 0.05), nuclear factor κB (NF-κB) (P < 0.01), NLR family pyrin domain containing 3 (NLRP3) (P < 0.01), caspase-1 (P < 0.01), interleukin 1β (IL-1β) (P < 0.05) and IL-18 (P < 0.01) in the jejunum tissues of the weaned pigs. The expression of NLRP3 (P < 0.05), caspase-1 (P < 0.01), IL-1β (P < 0.05) and IL-18 (P < 0.05) was also reduced in the ileum tissues of the weaned pigs. These results showed that L. acidophilus supplementation improves the growth performance, enhances the intestinal physical barrier function, and inhibits the expression of NOD1 and NLRP3 signaling-pathway-related genes in jejunum and ileum tissues. They also suggest that L. acidophilus enhances the intestinal physical barrier functioning by inhibiting IL-1β and IL-18 pro-inflammatory cytokines via the NOD1/NLRP3 signaling pathway in weaned piglets.

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Lijing Yan ◽  
Xia Xu ◽  
Zhenyu He ◽  
Sheng Wang ◽  
Linlin Zhao ◽  

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

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