Plasma Concentration Of Lipopolysaccharide Research Articles

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1β and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-β (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1β (IL-1β) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107days. On day 7, experimental AP was induced in the AP groups, and after 70days, MEL (5mg/kg) was administered to the MEL groups for 30days. Plasma concentrations of LPS and IL-1β were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1β plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1β and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Detection of endotoxin in plasma of hospitalized diarrheic calves.

To investigate whether lipopolysaccharide (LPS) is present in plasma of calves with naturally occurring diarrhea. The second objective was to determine whether plasma [LPS] correlates with clinical, hematological, biochemical, and acid-base variables, and whether [LPS] differs between surviving and nonsurviving diarrheic calves. Prospective observational study (January 2012-May 2014). Veterinary teaching hospital. Thirty-four calves <28 days old admitted for diagnosis and treatment of diarrhea and 30 healthy control calves. Admission demographics, physical examination, blood gas, biochemistry analysis, and outcome data were recorded. Plasma concentration of LPS was determined using a bovine LPS ELISA assay. Plasma [LPS] was detected in both healthy and diarrheic calves. Plasma [LPS] was significantly higher in diarrheic than healthy calves (median: 0.99ng/mL; Interquartile range (IQR): 0.068, vs 0.88ng/mL; 0.065ng/mL, respectively; P < 0.001). Plasma [LPS] was higher in nonsurviving (1.04ng/mL; 0.07ng/mL) than in surviving calves (0.98ng/mL; 0.022ng/mL; P < 0.001). Plasma [LPS] was higher in beef (1.07ng/mL; 0.182ng/mL) than in dairy diarrheic calves (0.99ng/mL; 0.022ng/mL; P < 0.001). In diarrheic calves, plasma [LPS] correlated with [l-lactate] (r2 = 0.496; P = 0.002); hypoglycemia (r2 = -0.453; P = 0.007); increased unmeasured strong ions (r2 = 0.332; P = 0.050), [Mg2+ ] (r2 = 0.475; P = 0.004), and [phosphate] (r2 = 0.468; P = 0.005), and increased aspartate aminotransferase activity (r2 = 0.348; P = 0.003). This study highlights a potential role of LPS in the pathogenesis of metabolic derangements such as hyperlactatemia, hypoglycemia, and increased concentration of unmeasured strong anions in diarrheic calves. Further investigation evaluating the effect of LPS on l-lactate and glucose metabolism in diarrheic calves is warranted.

Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats.

To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD). Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined. The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine. JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.

The Role of LPS-TLR4 Pathway on Hepatic Fibrogenesis in Chronic Ethanol-Fed Rats

Introduction: Gut-derived lipopolysaccharide (LPS) has been proposed as a key player in the pathogenesis of alcoholic liver disease (ALD). The aims of this study were to investigate the role of LPS on hepatic fibrogenesis in a rat model of chronic alcohol feeding. Methods: Forty-eight Sprague-Dawley male rats were randomly divided as 4 groups and fed isocaloric Liber-DeCarli liquid diets ± alcohol (36% of total caloric value) for 8 weeks or 10 weeks. Plasma concentrations of LPS in portal veins from these rats were determined by spectrophotometric method. Rat liver tissue samples were examined for TLR4 and TGF-β1 mRNA by in situ hybridization. Immunohistochemistry was used to determine FSP-1 and vimentin for identification of activated HSC while F4/80 for recognition of Kuffer cells in serial sections of liver tissues. Computer image analysis was performed to measure the integrated optimal density (IOD) of FSP-1-positive HSC and TLR4 mRNA-positive cells. Hepatic collagen-I and α-SMA protein were analyzed by Western blot while IL-1, IL-6, TNF-α, and TGFβ1 mRNA were accessed by RT-PCR. Histological characteristics were evaluated by H and E staining and Masson’s Trichrome stain. Results: Masson’s Trichrome stain showed that there was a perisinusoidal fibrosis in rats fed ethanol at the end of 10 weeks, which was consistent with increased expression of collagen I by Western blot. Immunohistochemical stain showed there were abundant activated HSCs and some Kuffer cells in livers of rats fed ethanol at the end of 10 weeks, but a few HSC were seen in control-diet fed rats. Plasma LPS levels in portal veins were significantly higher in 10-week alcohol-fed rats than in 10-week controldiet-fed rats, but LPS levels were not increased in 8-week alcohol-fed rats. In situ hybridization analysis showed that a significant increase of TLR4 mRNA could be detected in abundant hepatocytes and some activated HSC and Kuffer cells in 10-week alcohol-fed rat livers, but in fewer endothelial cells of central vein in control-diet-fed rats. Bivariate correlation analysis showed that there was a positive correlation between the expression intensity of TLR4 mRNA in livers and the levels of plasma LPS in the portal vein of 10-week alcohol-fed rats (r=0.856; p<0.05); furthermore, the expressions of proinflammatory cytokine mRNA, including IL-1, IL-6, and TNF-α, as well as profibrogenic factor TGF-β1 mRNA, were increased in livers of 10-week alcohol-fed rats compared with control diet-fed rats. Conclusion: This study highlights the role of gut-derived LPS on hepatic fibrogenesis in a rat model of chronic alcohol feeding.

Neither Microbial Translocation Nor TLR Responsiveness Are Likely Explanations for Preexisting Immune Activation in Women Who Subsequently Acquired HIV in CAPRISA 004

Innate immune activation was a strong predictor of HIV acquisition in women at risk for HIV in CAPRISA 004. Identifying the cause(s) of activation could enable targeted prevention interventions. In this study, plasma concentrations of lipopolysaccharide, soluble CD14, and intestinal fatty acid-binding protein did not differ between subjects who did or did not subsequently acquire HIV nor were these levels correlated with plasma cytokines or natural killer cell activation. There was no difference between HIV acquirers and non-acquirers in the chemokine and cytokine responses of peripheral blood mononuclear cells stimulated with TLR2, 4, or 7/8 agonists. Further studies are required.

Increased Microbial Translocation in ≤180 Days Old Perinatally Human Immunodeficiency Virus-positive Infants as Compared With Human Immunodeficiency Virus-exposed Uninfected Infants of Similar Age

The effect of early versus deferred antiretroviral treatment (ART) on plasma concentration of lipopolysaccharide (LPS) and host LPS-binding molecules in human immunodeficiency virus (HIV)-infected infants up to 1 year of age was investigated. We evaluated 54 perinatally HIV-infected and 22 HIV-exposed uninfected infants (controls) at the first and second semester of life. All HIV-infected infants had a baseline CD4 of ≥ 25%, participated in the Comprehensive International Program of Research on AIDS Children with HIV Early Antiretroviral Therapy trial in South Africa, and were randomized in the following groups: group 1 (n = 20), ART deferred until CD4 < 25% or severe HIV disease; and group 2 (n = 34), ART initiation within 6 to 12 weeks of age. LPS, endotoxin-core antibodies, soluble CD14 (sCD14), and LPS-binding protein (LBP) were measured in cryopreserved plasma. T-cell activation was measured in fresh whole blood. At the first semester, LPS concentration was higher in HIV-infected infants than in controls; sCD14, LBP, and T-cell activation were higher in group 1 than in group 2 and controls. Although LPS was not correlated with study variables, viral load was positively associated with sCD14, LBP, or endotoxin-core antibodies. At the second semester, LPS was not detectable and elevated host LPS-control molecules values were sustained in all groups and in conjunction with ART in all HIV-infected infants. Although plasma concentration of LPS was higher in perinatally HIV-infected infants 0 to 6 months of age than in controls independent of ART initiation strategy, concentration of LPS-control molecules was higher in infants with deferred ART, suggesting the presence of increased microbial translocation in HIV-infected infants with sustained early viral replication.

Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice

Diabetes and obesity are characterized by a low-grade inflammation whose molecular origin is unknown. We previously determined, first, that metabolic endotoxemia controls the inflammatory tone, body weight gain, and diabetes, and second, that high-fat feeding modulates gut microbiota and the plasma concentration of lipopolysaccharide (LPS), i.e., metabolic endotoxemia. Therefore, it remained to demonstrate whether changes in gut microbiota control the occurrence of metabolic diseases. We changed gut microbiota by means of antibiotic treatment to demonstrate, first, that changes in gut microbiota could be responsible for the control of metabolic endotoxemia, the low-grade inflammation, obesity, and type 2 diabetes and, second, to provide some mechanisms responsible for such effect. We found that changes of gut microbiota induced by an antibiotic treatment reduced metabolic endotoxemia and the cecal content of LPS in both high-fat-fed and ob/ob mice. This effect was correlated with reduced glucose intolerance, body weight gain, fat mass development, lower inflammation, oxidative stress, and macrophage infiltration marker mRNA expression in visceral adipose tissue. Importantly, high-fat feeding strongly increased intestinal permeability and reduced the expression of genes coding for proteins of the tight junctions. Furthermore, the absence of CD14 in ob/ob CD14(-)(/)(-) mutant mice mimicked the metabolic and inflammatory effects of antibiotics. This new finding demonstrates that changes in gut microbiota controls metabolic endotoxemia, inflammation, and associated disorders by a mechanism that could increase intestinal permeability. It would thus be useful to develop strategies for changing gut microbiota to control, intestinal permeability, metabolic endotoxemia, and associated disorders.

INFLUENCE OF ROUTE OF ADMINISTRATION ON HEMODYNAMIC EFFECTS OF ENDOTOXIN.

The effect of route of administration of endotoxin upon subsequent hemodynamic events was evaluated in a perfused canine small intestinal preparation. One ld50 of Shigella flexneri endotoxin was injected into either the superior mesenteric artery (6 animals), a mesenteric vein (6 animals), or the right femoral vein (6 animals). Pressures were monitored in the superior mesenteric artery, a mesenteric vein, and the left femoral artery for 30 min after injection of endotoxin. In the three groups of dogs the same qualitative effects were observed: portal venous hypertension, systemic arterial hypotension, and an increase in small intestinal vascular resistance. However, portal hypertension was greatest when endotoxin was injected into the portal circulation, systemic arterial hypotension was most profound when endotoxin was injected into a femoral vein, and mesenteric vascular resistance was most prolonged when endotoxin was injected into the mesenteric artery. These findings suggest that the hemodynamic response of a regional vascular bed to endotoxin is influenced by the initial plasma concentration of lipopolysaccharide.