scholarly journals Dietary Curcumin Alleviated Aflatoxin B1-Induced Acute Liver Damage in Ducks by Regulating NLRP3–Caspase-1 Signaling Pathways

Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3086
Author(s):  
Sanjun Jin ◽  
Hao Yang ◽  
Yingjie Wang ◽  
Qian Pang ◽  
Yihan Jiao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Dna Adducts ◽  
Liver Damage ◽  
Aflatoxin B1 ◽  
Control Group ◽  
Oxidation Stress ◽  
Basic Diet ◽  
Caspase 1

Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in animal feed and human food; it represents a serious threat to human and animal health. This study investigates the mechanism by which dietary curcumin protected liver against acute damage caused by AFB1 administration in ducks. One-day-old male ducks (n = 450) were randomly assigned to three groups, the control group, the AFB1 group, and the AFB1 + curcumin group; the first group were fed with basic diet, while the third group was fed basic diet containing 500 mg/kg curcumin. Ducks in the AFB1 group and AFB1 + curcumin group were challenged with AFB1 at the age of 70 days. The results show that AFB1 administration caused liver damage, increased CYP450 content and AFB1-DNA adducts in the liver, and induced oxidative stress and inflammatory response in the liver. Dietary curcumin significantly inhibited the generation of H2O2 and MDA in liver, activated the Nrf2-ARE signaling pathway, and suppressed the NLRP3–caspase-1 signaling pathway in the liver of ducks. Conclusively, curcumin in diet could protect duck liver against the generation of AFB1-DNA adducts, toxicity, oxidation stress and inflammatory response induced by AFB1 through regulating the NLRP3–caspase-1 signaling pathways, demonstrating that curcumin is a potential feed additive agent to reduce the serious harmful effects of AFB1 on duck breeding.

scholarly journals Dietary Curcumin Alleviated Acute Ileum Damage of Ducks (Anas platyrhynchos) Induced by AFB1 through Regulating Nrf2-ARE and NF-κB Signaling Pathways

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1370
Author(s):  
Sanjun Jin ◽  
Hao Yang ◽  
Yihan Jiao ◽  
Qian Pang ◽  
Yingjie Wang ◽  
...  
Keyword(s):  
Body Weight ◽  
Signaling Pathway ◽  
Dna Adducts ◽  
Animal Feed ◽  
Control Group ◽  
Toxic Metabolite ◽  
Oxidation Stress ◽  
Similar Weight ◽  
Underlying Mechanisms ◽  
Anti Inflammation

Aflatoxin B1 (AFB1) is a stable toxic metabolite threatening health of human and animal and widely contaminated animal feed and human food. This present study aimed to investigate the effects of dietary curcumin on ileum injury in ducks induced by AFB1 administration and explore its underlying mechanisms. Ducks (N = 450, one-day-old male) with a similar weight were randomly assigned to 3 groups, containing the control group, AFB1 group (60 μg AFB1 kg−1 body weight) and curcumin (500 mg curcumin kg−1 diet) + AFB1 group. AFB1 administration markedly increased the ileum damage, AFB1-DNA adducts in the plasma and oxidation stress and inflammation. Adding curcumin into diet protected the ileum against morphology damage induced by AFB1 administration, decreased AFB1-DNA adducts in the plasma and eliminated oxidation stress and inflammation in the ileum of ducks. Anti-oxidation and anti-inflammatory effects of curcumin could protect the ileum against acute damage via activating Nrf2-ARE signaling pathway and inhibiting NF-κB signaling pathway. Conclusively, curcumin was a dietary anti-oxidation and anti-inflammation agent via activating Nrf2-ARE signaling pathway and inhibiting NF-κB signaling pathway to protect ileum against acute damage induced by AFB1 administration.

scholarly journals Umbelliferone ameliorates ulcerative colitis induced by acetic acid via modulation of TLR4/NF-κB-p65/iNOS and PPARγ/SIRT1 signaling pathways in rats

2021 ◽  
Author(s):  
Basel A Abdel-Wahab ◽  
Saad A Alkahtani ◽  
Abdulsalam A Alqahtani ◽  
Emad H.M. Hassanein
Keyword(s):  
Ulcerative Colitis ◽  
Acetic Acid ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Oxidative Injury ◽  
Control Group ◽  
Anti Inflammatory

Abstract Ulcerative colitis (UC) is a common chronic, idiopathic inflammatory bowel disease associated with inflammatory perturbation and oxidative stress. Umbelliferone (UMB) is a potent anti-inflammatory and antioxidant coumarin derivative. Depending on the possible mechanisms, we aimed to explore and elucidate the therapeutic potential of UMB on UC-inflammatory response and oxidative injury-induced via intrarectal administration of acetic acid (AA). Rats were assigned into four groups: control group, UMB (30 mg/kg) treated group, colitis model group (2 ml of AA; 3% v/v), and colitis treated with UMB groups. Our results exhibited that UMB improved macroscopic and histological tissue injury caused by the AA. Mechanistically, UMB reduced the elevated TNF-α, IL-6, MPO and VCAM-1 via effective downregulation of TLR-4, NF-κB and iNOS signaling pathway, thereby mediated potent anti-inflammatory effects. Moreover, UMB administration resulted in effective up-regulation of both PPARγ and SIRT1 signaling pathways, thereby inhibited both oxidative injury and inflammatory response. Conclusively, UMB protected against AA-induced UC in rats through suppressing of the TLR4/NF-κB-p65/iNOS signaling pathway and promoting the PPARγ/SIRT1 signaling. Indeed, our data proved the effectiveness of UMB in UC and introduced it as a potential therapeutic beneficial applicant for clinical application.

Glia Maturation Factor-Gamma Negatively Modulates TLR4 Signaling In Macrophages Induced by Lipopolysaccharide (LPS).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1482-1482
Author(s):  
Wulin Aerbajinai ◽  
Kyung Chin ◽  
Hyun Woo Lee ◽  
Jianqiong Zhu ◽  
Griffin P. Rodgers
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Luciferase Assay ◽  
Enzyme Linked Immunosorbent Assay ◽  
Glia Maturation Factor ◽  
Tlr4 Signaling ◽  
Maturation Factor ◽  
Nf Kappab

Abstract Abstract 1482 Toll-like receptor 4 (TLR4) plays a critical role in innate immunity that recognize pathogenic molecules and trigger inflammatory response. However, excessive activation of TLR4 activation may contribute to pathogenesis of autoimmune and inflammatory diseases. Therefore, the negative regulation of TLR4-triggered inflammatory response attracts much attention in recent years. Activation of TLR4 signaling pathways by lipopolysaccharide (LPS) leads to the production of a broad array of cytokines and mediators that coordinate the immune response in macrophages. Glia maturation factor gamma (GMFG), a member of the ADF/cofilin family of proteins that regulate actin cytoskeleton reorganization, is preferentially expressed in inflammatory cells, but its function in macrophages immune response remains unclear. In this study, we investigated whether GMFG participates in the molecular events underlying the inflammatory reaction to LPS in macrophages by knockdown of GMFG using small-interfering RNA approach. We show here that knockdown of GMFG significantly enhanced LPS-induced production of proinflammatory cytokines and chemokines, including TNF-alpha, IL-1beta, IL-8, and MCP-1 in human peripheral blood monocytes-derived macrophage as determined by quantitative real time-PCR and confirmed by enzyme-linked immunosorbent assay. Silencing of GMFG expression potentiates LPS-induced activation of p38, ERK1/2 and NF-kappaB signaling pathways by Western blot analysis. Moreover, luciferase assay revealed that gene silencing of GMFG promoted LPS-induced NF-kappaB activity for ∼2.5- to 4-fold. Furthermore, we found that TLR4 protein expression level were higher in GMFG-silenced macrophage compared with that of the control siRNA-transfected macrophages after stimulated with LPS for 1 hour. These results suggest that GMFG negatively regulation of TLR4 signaling-induced inflammatory cytokines by modulation of TLR4 expression levels and its down-stream NF-kappaB and p38 MAPK signaling pathway. In summary, we report that GMFG, in macrophage, function as a novel negative regulator that participates in the regulation of TLR4-signaling pathway, implicating that macrophage-specific modulation of GMFG may be beneficial in the treatment of inflammation as well as autoimmune disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Monocytes Undergo Functional Reprogramming to Generate Immunosuppression through HIF-1α Signaling Pathway in the Late Phase of Sepsis

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Li-Li Li ◽  
Bing Dai ◽  
Yu-Han Sun ◽  
Ting-Ting Zhang
Keyword(s):  
Clinical Study ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Animal Study ◽  
Inflammatory Responses ◽  
Late Phase ◽  
Severe Pneumonia ◽  
Control Group ◽  
L1 Protein ◽  
Control Injection

Severe pneumonia with sepsis is characterized by a dysregulated inflammatory response of endotoxin. In our study, we attempted to investigate the roles of the immune guardian cells (monocytes) in the immune-inflammatory response of severe pneumonia-induced sepsis. We performed analysis in the blood samples of human and animals with ELISA, western blot, flow cytometry (FCM) methods, etc. Results showed that the proinflammatory status shifted to hypoinflammatory phases during the sepsis process. In a clinical study, the levels of IL-1β, IL-6, TNF-α, etc., except for IL-10, were inhibited in the late phase of sepsis, while, in an animal study, the immune suppression status was attenuated with administration of the adenovirus Ade-HIF-1α. Conversely, the amount of IL-10 was lower in the adenovirus Ade-HIF-1α group compared with the sepsis model group and the Ade-control group. Moreover, in the clinical study, the programmed cell death-ligand 1 (PD-L1) was overexpressed in monocytes in the late phase of sepsis, while the expression of proteins HIF-1α and STAT3 was decreased in the late phase of sepsis. However, in the animal study, we found that the HIF-1α factor facilitated the inflammatory response. The expression of the proteins HIF-1α and STAT3 was increased, and the PD-L1 protein was decreased with the adenovirus Ade-HIF-1α administration compared with the rats without Ade-HIF-1α injection and with the Ade-control injection. Additionally, the proteins HIF-1α and STAT3 were coregulated at transcriptional levels during the inflammatory responses of sepsis. Taken together, monocytes undergo reprogramming to generate immunosuppression through the HIF-1α signaling pathway in the late phase of sepsis.

scholarly journals IL-38 restrains inflammatory response of collagen-induced arthritis in rats via SIRT1/HIF-1α signaling pathway

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Bing Pei ◽  
Keyan Chen ◽  
Shenglai Zhou ◽  
Dongyu Min ◽  
Weiguo Xiao
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Joint Damage ◽  
Inhibitory Effect ◽  
Angiogenic Factor ◽  
Inflammatory Factors ◽  
Control Group ◽  
Collagen Induced Arthritis ◽  
Related Proteins

Abstract Objective: To observe the restraining effect of IL-38 on inflammatory response in collagen-induced arthritis rats (CIA), and to explore the regulatory mechanism of SIRT1/HIF-1α signaling pathway. Methods: 40 SD rats were randomly divided into Control group, CIA group, CLL group and CLH group, with 10 rats in each group; CIA rat model was established. The effects of IL-38 on arthritis index, inflammatory response, osteogenic factor and angiogenic factor were observed by methods including HE staining, ELISA, immunohistochemical and immunofluorescence. Human synoviocytes were cultured in vitro, and SIRT1 inhibitors were added to detect the expression for relating factors of SIRT1/HIF-1α signaling pathway by Western blot. Results: IL-38 could alleviate CIA joint damage and restrain inflammatory response, could up-regulate the expression of OPG in CIA rats and could down-regulate the expression of RANKL and RANK. IL-38 could restrain the expression of VEGF, VEGFR1, VEGFR2 and HIF. Moreover, we found that IL-38 could up-regulate the SIRT1 expression and down-regulate the HIF-1α, TLR4 and NF-KB p65 expression in CLL and CLH groups. From the treatment of synoviocytes to simulate the CIA model and the treatment of SIRT1 inhibitors, we demonstrated that the inhibitory effect of IL-38 on inflammatory factors and regulation of SIRT1/HIF-1α signaling pathway-related proteins were inhibited. Conclusion: IL-38 can restrain the inflammatory response of CIA rats, can promote the expression of osteogenic factors, can inhibit neovascularization, and can alleviate joint damage in rats. The mechanism may be related to the regulation of SIRT1/HIF-1α signaling pathway.

scholarly journals Protective Effects of MicroRNA-126 on Human Cardiac Microvascular Endothelial Cells Against Hypoxia/Reoxygenation-Induced Injury and Inflammatory Response by Activating PI3K/Akt/eNOS Signaling Pathway

2017 ◽  
Vol 42 (2) ◽  
pp. 506-518 ◽  
Author(s):  
Hong-Hui Yang ◽  
Yan Chen ◽  
Chuan-Yu Gao ◽  
Zhen-Tian Cui ◽  
Jian-Min Yao
Keyword(s):  
Cell Proliferation ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Control Group ◽  
Protective Effects ◽  
Enos Expression ◽  
Lumen Formation ◽  
Tnf Α ◽  
Cardiac Microvascular Endothelial Cells

Objective: This study explored the protective effects of the microRNA-126 (miR-126)-mediated PI3K/Akt/eNOS signaling pathway on human cardiac microvascular endothelial cells (HCMECs) against hypoxia/reoxygenation (H/R)-induced injury and the inflammatory response. Methods: Untreated HCMECs were selected for the control group. After H/R treatment and cell transfection, the HCMECs were assigned to the H/R, miR-126 mimic, mimic-negative control (NC), miR-126 inhibitor, inhibitor-NC, wortmannin (an inhibitor of PI3K) and miR-126 mimic + wortmannin groups. Super oxide dismutase (SOD), nitric oxide (NO), vascular endothelial growth factor (VEGF) and reactive oxygen species (ROS) were measured utilizing commercial kits. Quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were performed to detect miR-126 expression and the mRNA and protein expression of inflammatory factors. Western blotting was used to determine the expression of key members in the PI3K/Akt/eNOS signaling pathway. ACCK-8 assay and flow cytometry were employed to examine cell proliferation and apoptosis, respectively. The angiogenic ability in each group was detected by the lumen formation test. Results: Compared to the control group, p/t-PI3K, p/t-Akt and p/t-eNOS expression, NO, VEGF and SOD levels, cell proliferation and in vitro lumen formation ability were decreased, while the ROS content, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α expression and cell apoptosis were significantly increased in the H/R, mimic-NC, miR-126 inhibitor, inhibitor-NC, wortmannin and miR-126 mimic + wortmannin groups. Additionally, in comparison with the H/R group, the miR-126 mimic group had elevated p/t-PI3K, p/t-Akt and p/t-eNOS expression, increased NO, VEGF and SOD contents, and strengthened cell proliferation and lumen formation abilities but also exhibited decreased ROS content, reduced IL-6, IL-10 and TNF-α expressions, and weakened cell apoptosis, while the miR-126 inhibitor and wortmannin group exhibited the opposite results. Furthermore, decreased p/t-PI3K, p/t-Akt and p/t-eNOS expressions, decreased NO, VEGF and SOD contents, cell proliferation and lumen formation abilities, as well as increased ROS content, increased IL-6, IL-10 and TNF-α expression, and increased cell apoptosis were observed in the miR-126 mimic + wortmannin group compared to themiR-126 mimic group. Conclusions: These findings indicated that miR-126 protects HCMECs from H/R-induced injury and inflammatory response by activating the PI3K/Akt/ eNOS signaling pathway.

scholarly journals Resveratrol Relieved Acute Liver Damage in Ducks (Anas platyrhynchos) Induced by AFB1 via Modulation of Apoptosis and Nrf2 Signaling Pathways

Animals ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 3516
Author(s):  
Fangju Liu ◽  
Yingjie Wang ◽  
Xin Zhou ◽  
Mengru Liu ◽  
Sanjun Jin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Damage ◽  
Biological Activities ◽  
Control Group ◽  
Related Factor ◽  
Acute Liver Damage ◽  
Basic Diet ◽  
Significant Difference ◽  
Specific Pathogen ◽  
Male Specific

The presence of aflatoxin B1 (AFB1) in feed is a serious threat to livestock and poultry health and to human food safety. Resveratrol (Res) is a polyphenolic compound with antioxidant, anti-apoptotic and other biological activities; however, it is not clear whether it can improve AFB1 induced hepatotoxicity. Therefore, this study was conducted to investigate the effects of dietary Res on liver injury induced by AFB1 and its mechanisms. A total of 270 one-day-old male specific pathogen free (SPF) ducks, with no significant difference in weight, were randomly assigned to three groups: the control group, the AFB1 group and the AFB1 + Res group, which were fed a basic diet, a basic diet and a basic diet containing 500 mg/kg Res, respectively. On the 70th day, the ducks in theAFB1 group and the AFB1+ 500 mg/kg Res group were given 60 μg/kg AFB1 via gavage. When comparing the AFB1 group and the AFB1 + Res group and also with the control group, AFB1 significantly increased liver damage, cytochrome P450 (CYP450) and AFB1-DNA adduct content, increased oxidative stress levels and induced liver apoptosis, which was improved by Res supplementation. In sum, the addition of Res to feed can increase the activity of the II-phase enzyme, activate the nuclear factor E2-related factor 2 (Nrf2) signal pathway, and protect ducks’ livers from the toxicity, oxidative stress and inflammatory reaction induced by AFB1.

scholarly journals N-acetyl-L-tryptophan attenuates hepatic ischemia-reperfusion injury via regulating TLR4/NLRP3 signaling pathway in rats

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11909
Author(s):  
Yitong Pan ◽  
Shuna Yu ◽  
Jianxin Wang ◽  
Wanzhen Li ◽  
Huiting Li ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Control Group ◽  
Hepatic Ischemia ◽  
Caspase 1 ◽  
Hepatic Ischemia Reperfusion

The aim of this study was to investigate the changes of TLR4/NLRP3 signal during hepatic ischemia-reperfusion injury (HIRI) and to verify whether N-acetyl-L-tryptophan (L-NAT) protected hepatocytes by regulating the activation of TLR4/NLRP3 signal. We have established the rat HIRI model and H2O2-induced cell damage model to simulate ischemia-reperfusion injury and detect the corresponding indicators. Compared with the sham group, Suzuki score and the level of serum ALT increased after HIRI, accompanied by an increased expression of NLRP3, ASC, Caspase-1, IL-1β, TLR4, and NF-κB. While L-NAT pretreatment reversed the above-mentioned changes. Compared with the control group, cells in the H2O2 treated group became smaller in cell volume and round in shape with unclear boundaries. Similar to the phenotypes in vivo, H2O2 treatment also induced significant increase in expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 and IL-1β) and inflammatory factors (TLR4 and NF-κB). While L-NAT pretreatment attenuated injuries caused by H2O2. In conclusion, the present findings demonstrate that L-NAT alleviates HIRI by regulating activation of NLRP3 inflammasome, which may be related to the TLR4/NF-κB signaling pathway.

scholarly journals Effects of dietary supplementation with Lactobacillus acidophilus on the performance, intestinal physical barrier function, and the expression of NOD-like receptors in weaned piglets

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e6060 ◽  
Author(s):  
Shiqiong Wang ◽  
Haihua Li ◽  
Chenhong Du ◽  
Qian Liu ◽  
Dongji Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lactobacillus Acidophilus ◽  
Barrier Function ◽  
Dietary Supplementation ◽  
Control Group ◽  
Mrna Levels ◽  
Physical Barrier ◽  
Weaned Piglets ◽  
Weaned Pigs ◽  
Caspase 1

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.

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