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Ameliorative effects of supranutritional selenium on TLR-4-NF-kB-TNF-α-mediated hepatic oxidative injury and inflammation in goats fed high concentrate diet.

ABSTRACT: We examined whether surplus dietary selenium (Se) supply could alleviate high concentrate (HC) diet-induced hepatic oxidative stress (OS) and inflammation. Eighteen young goats were distributed into three groups; were fed low (LC, concentrate: forage; 35: 65), high concentrate (HC, 65: 35), or Se-supplemented HC (HCSe, 65: 35 + 0.5 mg Se kg^-1 diet) diets for 10 weeks. Short chain fatty acids, OS markers and immunoinflammatory genes expressions were assessed through gas chromatograph, kits, and RT-qPCR, respectively. Compared with LC, HC diet increased (p < .05) colonic and serum lipopolysaccharide (LPS) levels and induced hepatic oxidative injury by increasing (p < .05) malondialdehyde (MDA) levels and decreasing (p < .05) activities of glutathione peroxidase, superoxide dismutase, and catalase. HC diet altered hepatic mRNA expressions of toll-like receptor-4 (TLR-4), cluster of differentiation-14 (CD-14), tumor necrosis factor-α (TNF-α), TNF receptor-associated factor-6 (TRAF-6), nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), IL-10, IL-13, LPS-binding protein (LBP), serum amyloid A (SAA), α-acid glycoprotein (AGP), and albumin (ALB). Conversely, extra-Se supply lowered LPS and attenuated antioxidant status and inflammation in liver. In conclusion, HC diet induced oxidative lesions and TLR-4 pathway-mediated inflammation, whereas supranutritional Se alleviated oxidative and inflammatory lesions through TLR-4 pathway regulation in goat liver.

SUBMITTER: Shah T

PROVIDER: S-EPMC9632208 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Ameliorative effects of supranutritional selenium on TLR-4-NF-kB-TNF-α-mediated hepatic oxidative injury and inflammation in goats fed high concentrate diet.

Shah Tahmina T Malhi Moolchand M Kachiwal Allah Bux AB Bhutto Bachal B Shah Qurban Ali QA Lei Yan Y Soomro Saeed Ahmed SA Soomro Jamila J Kalhoro Nazeer Hussain NH Gui Hongbing H

Food science & nutrition 20220718 11

We examined whether surplus dietary selenium (Se) supply could alleviate high concentrate (HC) diet-induced hepatic oxidative stress (OS) and inflammation. Eighteen young goats were distributed into three groups; were fed low (LC, concentrate: forage; 35: 65), high concentrate (HC, 65: 35), or Se-supplemented HC (HCSe, 65: 35 + 0.5 mg Se kg<sup>-1</sup> diet) diets for 10 weeks. Short chain fatty acids, OS markers and immunoinflammatory genes expressions were assessed through gas chromatograph, ...[more]

PMID: 36348775

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Project description:BackgroundHigh concentrate (HC) diet-induced oxidative stress causes gut epithelial damages associated with apoptosis. Selenium (Se) being an integral component of glutathione peroxidase (GSH-Px) plays an important role in antioxidant defense system. Therefore, increasing dietary Se level would alleviate HC diet-induced injuries in gut mucosa. The present study investigated eighteen cross-bred goats, randomly divided into three groups (n = 6/group) fed either low concentrate (LC, roughage: concentrate ratio 65:35), high concentrate (HC, 35:65) or HC plus Se (HC-SY) diets for 10 weeks. Se was supplemented at the dose rate of 0.5 mg Se kg- 1 diet in the form of selenium yeast. The background Se level in HC and LC diets were 0.15 and 0.035 mg.kg- 1 diet, respectively. The Se at the dose of 0.115 mg.kg- 1 diet was added in LC diet to make its concentration equivalent to HC diet and with the supplementation of 0.5 mg Se kg- 1, the goats in group HC-SY received total Se by 0.65 mg.kg- 1 diet.ResultsThe molar concentrations of individual and total short chain fatty acids (TSCFA) significantly increased (P < 0.05) with simultaneous decrease in pH of colonic fluid in goats of HC and HC-SY groups compared with LC goats. HC diet induced loss of epithelial integrity, inflammation and loss of goblet cells in colonic mucosa associated with higher lipopolysaccharide (LPS) concentrations in colonic fluid whereas, the addition of SY in HC diet alleviated such damaging changes. Compared with LC, the HC diet elevated malondialdehyde (MDA) level with concurrent decrease in GSH-Px and superoxide dismutase (SOD) activities, while SY supplementation attenuated these changes and improved antioxidant status in colonic epithelium. Moreover, epithelial injury and oxidative stress in colon of HC goats were associated with increased apoptosis as evidenced by downregulation of bcl2 and upregulation of bax, caspases 3 and 8 mRNA expressions compared with LC goats. On contrary, addition of SY in HC (HC-SY) diet alleviated these changes by modulating expression of apoptotic genes in colonic epithelium.ConclusionsOur data suggest that supranutritional level of Se attenuates HC diet-induced oxidative stress and apoptosis and thereby minimizes the epithelial injury in colon of goats.

Project description:BackgroundSelenium (Se) is required for the synthesis of proteins (selenoproteins) with essential biological functions. Selenoproteins have a crucial role in the maintenance of cellular redox homeostasis in nearly all tissues, and are also involved in thyroid hormone metabolism, inflammation and immunity. Several immune processes rely on Se status and can be compromised if this element is present below the required level. Previous work has supported the notion that when Se is delivered at levels above those deemed to be the minimal required but below toxic concentrations it can have a boosting effect on the organism's immune response. Based on this concept Se-enriched supplements may represent a valuable resource for functional feeds in animal farming, including aquaculture.ResultsIn this study we tested the effects of Se supplemented as Sel-Plex during an immune challenge induced by polyinosinic:polycytidylic acid (poly(I:C)), a pathogen-associated molecular pattern (PAMP) that mimics viral infection. Trout were fed two diets enriched with 1 or 4 mg Se Kg(-1) of feed (dry weight) by Sel-Plex addition and a commercial formulation as control. The whole trout transcriptomic response was investigated by microarray and gene ontology analysis, the latter carried out to highlight the biological processes that were influenced by Sel-Plex supplementation in the head kidney (HK) and liver, the main immune and metabolic organs in fish. Overall, Sel-Plex enrichment up to 4 mg Se Kg(-1) induced an important response in the trout HK, eliciting an up-regulation of several genes involved in pathways connected with hematopoiesis and immunity. In contrast, a more constrained response was seen in the liver, with lipid metabolism being the main pathway altered by Se supplementation. Upon stimulation with poly(I:C), supplementation of 4 mg Se Kg(-1) increased the expression of principal mediators of the antiviral defences, especially IFN-γ, and down-stream molecules involved in the cell-mediated immune response.ConclusionsSupplementation of diets with 4 mg Se Kg(-1) using Sel-Plex remarkably improved the fish response to viral PAMP stimulation. Sel-Plex, being a highly bioavailable supplement of organic Se, might represent a suitable option for supplementation of fish feeds, to achieve the final aim of improving fish fitness and resistance against immune challenges.

Project description:Growing evidences suggest that sustained neuroinflammation, caused by microglia overactivation, is implicated in the development and aggravation of several neurological and psychiatric disorders. In some pathological conditions, microglia produce increased levels of cytotoxic and inflammatory mediators, such as tumor necrosis factor alpha (TNF-α), which can reactivate microglia in a positive feedback mechanism. However, specific molecular mediators that can be effectively targeted to control TNF-α-mediated microglia overactivation, are yet to be uncovered. In this context, we aim to identify novel TNF-α-mediated micro(mi)RNAs and to dissect their roles in microglia activation, as well as to explore their impact on the cellular communication with neurons. A miRNA microarray, followed by RT-qPCR validation, was performed on TNF-α-stimulated primary rat microglia. Gain- and loss-of-function in vitro assays and proteomic analysis were used to dissect the role of miR-342 in microglia activation. Co-cultures of microglia with hippocampal neurons, using a microfluidic system, were performed to understand the impact on neurotoxicity. Stimulation of primary rat microglia with TNF-α led to an upregulation of Nos2, Tnf, and Il1b mRNAs. In addition, ph-NF-kB p65 levels were also increased. miRNA microarray analysis followed by RT-qPCR validation revealed that TNF-α stimulation induced the upregulation of miR-342. Interestingly, miR-342 overexpression in N9 microglia was sufficient to activate the NF-kB pathway by inhibiting BAG-1, leading to increased secretion of TNF-α and IL-1β. Conversely, miR-342 inhibition led to a strong decrease in the levels of these cytokines after TNF-α activation. In fact, both TNF-α-stimulated and miR-342-overexpressing microglia drastically affected neuron viability. Remarkably, increased levels of nitrites were detected in the supernatants of these co-cultures. Globally, our findings show that miR-342 is a crucial mediator of TNF-α-mediated microglia activation and a potential target to tackle microglia-driven neuroinflammation.

Project description:Long-term supplementation of a high-concentrate diet enhances the accumulation of lactate and decrease in pH in goat rumen, thereby disrupting the composition of microbial community. Studies have shown that incorporation of thiamine in high-concentrate diet increases ruminal pH and decreases rumen lactate concentration. To explore the effects of thiamine supplementation with a high-concentrate diet on alteration of the whole ruminal microbiota and their metabolites, 18 mid-lactating Saanen goats were randomly fed with one of three diets: (1) control diet (CON; n = 6; concentrate:forage 30:70), (2) high-concentrate diet (HG; n = 6; concentrate:forage 70:30), and (3) high-concentrate diet with 200 mg of thiamine/kg of DMI (HGT; n = 6; concentrate:forage 70:30). The goats received experimental diets for 8 weeks. Ruminal samples were collected on the last day of the 8 weeks for 16S rRNA gene sequencing and the liquid chromatograph-mass spectrometer (LC-MS) analysis. The results revealed significant alterations of the ruminal bacterial community structure and diversity in HGT groups compared to HG groups, with an overall dominance of Bacteroidetes at the phylum level and Oribacterium (P < 0.05), Anaerobiospirillum (P < 0.01), and Fibrobacter (P < 0.01) at genus level in the HGT group. The LC-MS analysis revealed that thiamine supplementation resulted in lower levels of propionate (P < 0.05), pyruvate (P < 0.01), lactate (P < 0.05), putrescine (P < 0.05), tyramine (P < 0.05), and histamine (P < 0.01) and higher levels of acetate (P < 0.05), succinates (P < 0.01), oxaloacetic acid (P < 0.01), leucine (P < 0.01), valine (P < 0.05), linoleic acid (P < 0.05), docosahexaenoic acid (P < 0.05), and 4-phenylbutyric acid (P < 0.05) in the HGT group than in the HG group. The decrease in these compounds enhanced homeostasis in the rumen environment and suppressed epithelial inflammation. Correlation analysis revealed the potential relationships between ruminal metabolites and microbial community. These findings demonstrate that thiamine supplementation can alleviate subacute ruminal acidosis (SARA) by stabilizing the microbial community and reducing toxic unnatural compounds.

Project description:BACKGROUND:A promoter polymorphism in the pro-inflammatory cytokine tumor necrosis factor (TNF) (TNF G-308A) is associated with increased non-Hodgkin lymphoma (NHL) risk. The protein product, TNF-alpha, activates the nuclear factor kappa beta (NF-kappaB) transcription factor, and is critical for inflammatory and apoptotic responses in cancer progression. We hypothesized that the TNF and NF-kappaB pathways are important for NHL and that gene variations across the pathways may alter NHL risk. METHODOLOGY/PRINCIPAL FINDINGS:We genotyped 500 tag single nucleotide polymorphisms (SNPs) from 48 candidate gene regions (defined as 20 kb 5', 10 kb 3') in the TNF and TNF receptor superfamilies and the NF-kappaB and related transcription factors, in 1946 NHL cases and 1808 controls pooled from three independent population-based case-control studies. We obtained a gene region-level summary of association by computing the minimum p-value ("minP test"). We used logistic regression to compute odds ratios and 95% confidence intervals for NHL and four major NHL subtypes in relation to SNP genotypes and haplotypes. For NHL, the tail strength statistic supported an overall relationship between the TNF/NF-kappaB pathway and NHL (p = 0.02). We confirmed the association between TNF/LTA on chromosome 6p21.3 with NHL and found the LTA rs2844484 SNP most significantly and specifically associated with the major subtype, diffuse large B-cell lymphoma (DLBCL) (p-trend = 0.001). We also implicated for the first time, variants in NFKBIL1 on chromosome 6p21.3, associated with NHL. Other gene regions identified as statistically significantly associated with NHL included FAS, IRF4, TNFSF13B, TANK, TNFSF7 and TNFRSF13C. Accordingly, the single most significant SNPs associated with NHL were FAS rs4934436 (p-trend = 0.0024), IRF4 rs12211228 (p-trend = 0.0026), TNFSF13B rs2582869 (p-trend = 0.0055), TANK rs1921310 (p-trend = 0.0025), TNFSF7 rs16994592 (p-trend = 0.0024), and TNFRSF13C rs6002551 (p-trend = 0.0074). All associations were consistent in each study with no apparent specificity for NHL subtype. CONCLUSIONS/SIGNIFICANCE:Our results provide consistent evidence that variation in the TNF superfamily of genes and specifically within chromosome 6p21.3 impacts lymphomagenesis. Further characterization of these susceptibility loci and identification of functional variants are warranted.

Dataset Information

Ameliorative effects of supranutritional selenium on TLR-4-NF-kB-TNF-α-mediated hepatic oxidative injury and inflammation in goats fed high concentrate diet.

Publications

Ameliorative effects of supranutritional selenium on TLR-4-NF-kB-TNF-α-mediated hepatic oxidative injury and inflammation in goats fed high concentrate diet.

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