scholarly journals Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

2018 ◽  
Vol 9 (3) ◽  
pp. 389-399 ◽  
Author(s):  
M. Costanzo ◽  
V. Cesi ◽  
F. Palone ◽  
M. Pierdomenico ◽  
E. Colantoni ◽  
...  
Keyword(s):  
Vitamin D ◽  
Mrna Expression ◽  
Quantitative Pcr ◽  
Lactobacillus Reuteri ◽  
Clinical Score ◽  
Krill Oil ◽  
Histological Score ◽  
Tnf Α

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-α)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1β, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1β and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria.

scholarly journals In vitro and in vivo analyses of co-infections with peste des petits ruminants and capripox vaccine strains

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dajun Zhang ◽  
Bo Yang ◽  
Ting Zhang ◽  
Xijuan Shi ◽  
Chaochao Shen ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Quantitative Pcr ◽  
Small Ruminants ◽  
Infection Model ◽  
Peste Des Petits Ruminants ◽  
Immune Effect ◽  
Tnf Α ◽  
Antibody Levels

Abstract Background Peste des petits ruminants (PPR) and goat pox (GTP) are two devastating animal epidemic diseases that affect small ruminants. Vaccination is one of the most important measures to prevent and control these two severe infectious diseases. Methods In this study, we vaccinated sheep with PPR and POX vaccines to compare the changes in the antibody levels between animals vaccinated with PPRV and POX vaccines alone and those co-infected with both vaccines simultaneously. The cell infection model was used to explore the interference mechanism between the vaccines in vitro. The antibody levels were detected with the commercial ELISA kit. The Real-time Quantitative PCR fluorescent quantitative PCR method was employed to detect the viral load changes and cytokines expression after the infection. Results The concurrent immunization of GTP and PPR vaccine enhanced the PPR vaccine's immune effect but inhibited the immune effect of the GTP vaccine. After the infection, GTP and PPR vaccine strains caused cytopathic effect; co-infection with GTP and PPR vaccine strains inhibited the replication of PPR vaccine strains; co-infection with GTP and PPR vaccine strains enhanced the replication of GTP vaccine strains. Moreover, virus mixed infection enhanced the mRNA expressions of TNF-α, IL-1β, IL-6, IL-10, IFN-α, and IFN-β by 2–170 times. GTP vaccine strains infection alone can enhanced the mRNA expression of IL-1β, TNF-α, IL-6, IL-10, while the expression of IFN-α mRNA is inhibited. PPR vaccine strains alone can enhanced the mRNA expression of IFN-α, IFN-β, TNF-α, and has little effect the mRNA expression of IL-1β, IL-6 and IL-10. The results showed that GTP and PPR vaccine used simultaneously in sheep enhanced the PPR vaccine's immune effect but inhibited the immune effect of the GTP vaccine in vivo. Furthermore, an infection of GTP and PPR vaccine strains caused significant cell lesions in vitro; co-infection with GTP + PPR vaccine strains inhibited the replication of PPR vaccine strains, while the co-infection of GTP followed by PPR infection enhanced the replication of GTP vaccine strains. Moreover, virus infection enhanced the expressions of TNF-α, IL-1β, IL-6, IL-10, IFN-α, and IFN-β. Conclusions Peste des petits ruminants and capripox vaccine strains interfere with each other in vivo and vitro.

scholarly journals Bakuchiol Suppresses Inflammatory Responses Via the Downregulation of the p38 MAPK/ERK Signaling Pathway

2019 ◽  
Vol 20 (14) ◽  
pp. 3574 ◽  
Author(s):  
Hye-Sun Lim ◽  
Yu Jin Kim ◽  
Bu-Yeo Kim ◽  
Soo-Jin Jeong
Keyword(s):  
Mrna Expression ◽  
P38 Mapk ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mice Model ◽  
Tnf Α ◽  
Cox 2

The purpose of the present study was to evaluate the effects of bakuchiol on the inflammatory response and to identify the molecular mechanism of the inflammatory effects in a lipopolysaccharide (LPS)-stimulated BV-2 mouse microglial cell line and mice model. The production of prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay. The mRNA expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 was measured using reverse transcription–polymerase chain reaction analysis. Mitogen-activated protein kinase (MAPK) phosphorylation was determined by western blot analysis. In vitro experiments, bakuchiol significantly suppressed the production of PGE2 and IL-6 in LPS-stimulated BV-2 cells, without causing cytotoxicity. In parallel, bakuchiol significantly inhibited the LPS-stimulated expression of iNOS, COX-2, and IL-6 in BV-2 cells. However, bakuchiol had no effect on the LPS-stimulated production and mRNA expression of TNF-α or on LPS-stimulated c-Jun NH2-terminal kinase phosphorylation. In contrast, p38 MAPK and extracellular signal-regulated kinase (ERK) phosphorylation were inhibited by bakuchiol. In vivo experiments, Bakuchiol reduced microglial activation in the hippocampus and cortex tissue of LPS-injected mice. Bakuchiol significantly suppressed LPS-injected production of TNF-α and IL-6 in serum. These results indicate that the anti-neuroinflammatory effects of bakuchiol in activated microglia are mainly regulated by the inhibition of the p38 MAPK and ERK pathways. We suggest that bakuchiol may be beneficial for various neuroinflammatory diseases.

Vitamin D inhibits lipopolysaccharide-induced inflammatory response potentially through the Toll-like receptor 4 signalling pathway in the intestine and enterocytes of juvenile Jian carp (Cyprinus carpio var. Jian)

2015 ◽  
Vol 114 (10) ◽  
pp. 1560-1568 ◽  
Author(s):  
Jun Jiang ◽  
Dan Shi ◽  
Xiao-Qiu Zhou ◽  
Long Yin ◽  
Lin Feng ◽  
...  
Keyword(s):  
Vitamin D ◽  
Inflammatory Response ◽  
Mrna Expression ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Jian Carp ◽  
Pre Treatment ◽  
Inflammatory Effect

AbstractThe present study was conducted to investigate the anti-inflammatory effect of vitamin D both in juvenile Jian carp (Cyprinus carpio var. Jian) in vivo and in enterocytes in vitro. In primary enterocytes, exposure to 10 mg lipopolysaccharide (LPS)/l increased lactate dehydrogenase activity in the culture medium (P<0·05) and resulted in a significant loss of cell viability (P<0·05). LPS exposure increased (P<0·05) the mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8), which was decreased by pre-treatment with 1,25-dihydroxyvitamin D (1,25D3) in a dose-dependent manner (P<0·05). Further results showed that pre-treatment with 1,25D3 down-regulated Toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (Myd88) and NF-κB p65 mRNA expression (P<0·05), suggesting potential mechanisms against LPS-induced inflammatory response. In vivo, intraperitoneal injection of LPS significantly increased TNF-α, IL-1β, IL-6 and IL-8 mRNA expression in the intestine of carp (P<0·05). Pre-treatment of fish with vitamin D3 protected the fish intestine from the LPS-induced increase of TNF-α, IL-1β, IL-6 and IL-8 mainly by downregulating TLR4, Myd88 and NF-κB p65 mRNA expression (P<0·05). These observations suggest that vitamin D could inhibit LPS-induced inflammatory response in juvenile Jian carp in vivo and in enterocytes in vitro. The anti-inflammatory effect of vitamin D is mediated at least in part by TLR4-Myd88 signalling pathways in the intestine and enterocytes of juvenile Jian carp.

scholarly journals Rapamycin Attenuates Aldosterone-Induced Tubulointerstitial Inflammation and Fibrosis

2015 ◽  
Vol 35 (1) ◽  
pp. 116-125 ◽  
Author(s):  
Bin Wang ◽  
Wei Ding ◽  
Minmin Zhang ◽  
Hongmei Li ◽  
Yong Gu
Keyword(s):  
Mrna Expression ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Immunofluorescent Staining ◽  
Sprague Dawley ◽  
Mesenchymal Transition ◽  
Tnf Α ◽  
Tubulointerstitial Inflammation

Background/Aim: Aldosterone (Aldo), a mediator of kidney fibrosis, is implicated in the pathogenesis of chronic kidney diseases (CKD). The aim of this study was to evaluate the regulatory role of rapamycin (Rap) in Aldo-induced tubulointerstitial inflammation and fibrosis. Methods: Uninephrectomized, Sprague-Dawley rats were given 1% NaCl (salt) to drink and were randomized to receive treatment for 28 days as follows: vehicle infusion (control), 0.75 μg/h Aldo subcutaneous infusion, or Aldo infusion plus 1 mg/kg/day of Rap by intraperitoneal injection. The effect of Rap on Aldo-induced fibrosis and renal inflammation was investigated using Masson's technique, immunohistochemistry, and western blotting. The effects of Rap on the Aldo-induced epithelial-mesenchymal transition (EMT) process and on TNF-α mRNA expression and secretion in cultured HK-2 cells were investigated by immunofluorescent staining, western blot, qRT-PCR and ELISA. Results: An in vivo study indicated that signaling by the mammalian target of Rap (mTOR) was activated in rats in the Aldo group compared to controls, as indicated by up-regulated expression of p-mTOR and p-S6K. In addition, the inflammatory response increased, as evidenced by increases in inflammatory markers (MCP-1, ICAM-1, F4/80), and the accumulation of extracellular matrix (ECM), as indicated by increased collagen I and fibronectin expression and pro-fibrogenic gene (PAI-1 and TGF-β1) expression. These changes were attenuated by Rap treatment. An in vitro study showed that Rap significantly suppressed the Aldo-induced EMT process and TNF-α mRNA expression and secretion in cultured HK-2 cells. Conclusions: Rap can ameliorate tubulointerstitial inflammation and fibrosis by blocking mTOR signaling. Tubular cells may be a major cell type involved in this physiologic process.

Paricalcitol Effects on Activities and Metabolism of Platelet Activating Factor and on Inflammatory Cytokines in Hemodialysis Patients

2013 ◽  
Vol 36 (2) ◽  
pp. 87-96 ◽  
Author(s):  
Sophia N. Verouti ◽  
Alexandros B. Tsoupras ◽  
Fotini Alevizopoulou ◽  
Constantinos A. Demopoulos ◽  
Christos Iatrou
Keyword(s):  
Vitamin D ◽  
Blood Cells ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
Hemodialysis Patients ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Induced Aggregation

Purpose Paricalcitol improves the inflammatory status of hemodialysis patients. PAF is a strong inflammatory mediator which is produced during hemodialysis. We studied the effects of paricalcitol on PAF and other inflammatory mediators implicated in chronic kidney disease (CKD). Methods We examined the in vitro effects of paricalcitol on PAF/thrombin-induced aggregation as well as on the activities of PAF-basic metabolic enzymes, lyso-PAF acetyltransferase (Lyso-PAF-AT), DTT-insensitive CDP-choline: 1-alkyl-2-acetyl-sn-glycerol cholinephospho-transferase (PAF-CPT) and PAF-acetylhydrolase (PAF-AH) in blood cells from healthy volunteers. In addition, the in vivo effects of paricalcitol on the above these enzymes were examined in plasma and blood cells of hemodialysis patients who had not received any type of vitamin D treatment during the last three months before and after receiving paricalcitol for a month. Finally, IL-12p70, IL-1β, IL-6, IL-8 and TNF-α were measured. Results Paricalcitol inhibited in vitro PAF/thrombin-induced platelet aggregation and the inhibitory effect was comparable with that of PAF/thrombin antagonists. In addition, paricalcitol inhibited in vitro PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while much higher concentrations of paricalcitol were needed to inhibit Lyso-PAF-AT activity. Similarly, in hemodialysis patients, paricalcitol treatment reduced PAF-CPT activity in platelets and leukocytes and increased PAF-AH activity in leukocytes, while it could not influence Lyso-PAF-AT activity. On the other hand, paricalcitol therapy reduced IL-8, IL-1β, and TNF-α. Conclusions These results further support the beneficial effects of vitamin D treatment in hemodialysis patients, since it strongly affects PAF/thrombin activities, PAF-metabolism, and IL-8, IL-1β and TNF-α circulating levels.

scholarly journals Effect of TNF-α-Induced Sclerostin on Osteocytes during Orthodontic Tooth Movement

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Fumitoshi Ohori ◽  
Hideki Kitaura ◽  
Aseel Marahleh ◽  
Akiko Kishikawa ◽  
Saika Ogawa ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Osteoclast Formation ◽  
Rankl Expression ◽  
Bone Maintenance ◽  
Tnf Α

Osteocytes are abundant cells in bone, which contribute to bone maintenance. Osteocytes express receptor activator of nuclear factor kappa-B ligand (RANKL) and regulate osteoclast formation. Orthodontic tooth movement (OTM) occurs by osteoclast resorption of alveolar bone. Osteocyte-derived RANKL is critical in bone resorption during OTM. Additionally, tumor necrosis factor-α (TNF-α) is important in osteoclastogenesis during OTM. Sclerostin has been reported to enhance RANKL expression in the MLO-Y4 osteocyte-like cell line. This study investigated the effect of TNF-α on sclerostin expression in osteocytes during OTM. In vitro analysis of primary osteocytes, which were isolated from DMP1-Topaz mice by sorting the Topaz variant of GFP-positive cells, revealed that SOST mRNA expression was increased when osteocytes were cultured with TNF-α and that RANKL mRNA expression was increased when osteocytes were cultured with sclerostin. Moreover, the number of TRAP-positive cells was increased in osteocytes and osteoclast precursors cocultured with sclerostin. In vivo analysis of mouse calvariae that had been subcutaneously injected with phosphate-buffered saline (PBS) or TNF-α revealed that the number of TRAP-positive cells and the percentage of sclerostin-positive osteocytes were higher in the TNF-α group than in the PBS group. Furthermore, the level of SOST mRNA was increased by TNF-α. As an OTM model, a Ni-Ti closed-coil spring connecting the upper incisors and upper-left first molar was placed to move the first molar to the mesial direction in wild-type (WT) mice and TNF receptor 1- and 2-deficient (TNFRsKO) mice. After 6 days of OTM, the percentage of sclerostin-positive osteocytes on the compression side of the first molar in TNFRsKO mice was lower than that in WT mice. In this study, TNF-α increased sclerostin expression in osteocytes, and sclerostin enhanced RANKL expression in osteocytes. Thus, TNF-α may play an important role in sclerostin expression in osteocytes and enhance osteoclast formation during OTM.

In vitro C3 mRNA Expression in Pemphigus Vulgaris: Complement Activation is Increased by IL-1α and TNF-α

1999 ◽  
Vol 3 (3) ◽  
pp. 140-144 ◽  
Author(s):  
Claudio Feliciani ◽  
Paola Toto ◽  
Paolo Amerio ◽  
Pierluigi Amerio
Keyword(s):  
Mrna Expression ◽  
Complement Activation ◽  
In Vitro Study ◽  
Peak Level ◽  
Pemphigus Vulgaris ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Tnf Α

Background: Pemphigus vulgaris (PV) is a potentially life-threatening disease, characterized immunohistologically by IgG deposits and complement activation on the surface of keratinocytes. Complement activation has been implicated in the pathogenesis with C3 deposits in about 90% of patients. Objective: In order to further elucidate the role of complement in PV and to define which cytokines play a role in C3 mRNA expression, we performed an in vitro study in human keratinocytes. Methods: Normal human epidermal keratinocytes (NHuK) were incubated with PV serum and C3 mRNA was measured. We previously had shown that IL-1α and TNF-α are expressed in PV in vivo and in vitro. Since cytokines are able to modulate complement activation, mRNA expression was evaluated in a similar experiment after pretreatment using antibodies against IL-1α and TNF-α. Results: Incubation of NHuK with PV sera caused their detachment from the plates after 20–30 minutes with a complete acantholysis within 12 hours. An early C3 mRNA expression was seen after 30 minutes with a peak level after 1 hour. Blocking studies, using antibodies against human IL-1α and TNF-α in NHuK together with PV-IgG, showed reduction of in vitro induced acantholysis and inhibition of C3 mRNA expression. Conclusions: This study supports the hypothesis that complement C3 is important in PV acantholysis and that complement activation is increased by IL-1α and TNF-α.

scholarly journals Metformin and Vitamin D Modulate Inflammation and Autophagy during Adipose-Derived Stem Cell Differentiation

2021 ◽  
Vol 22 (13) ◽  
pp. 6686
Author(s):  
Sara Cruciani ◽  
Giuseppe Garroni ◽  
Renzo Pala ◽  
Maria Laura Cossu ◽  
Giorgio Carlo Ginesu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Adipogenic Differentiation ◽  
Stem Cell Differentiation ◽  
Low Grade ◽  
Mrna Levels ◽  
Tnf Α ◽  
Shock Proteins

Adipose-derived stem cells (ADSCs) came out from the regenerative medicine landscape for their ability to differentiate into several phenotypes, contributing to tissue regeneration both in vitro and in vivo. Dysregulation in stem cell recruitment and differentiation during adipogenesis is linked to a chronic low-grade inflammation and macrophage infiltration inside the adipose tissue, insulin resistance, cardiovascular disease and obesity. In the present paper we aimed to evaluate the role of metformin and vitamin D, alone or in combination, in modulating inflammation and autophagy in ADSCs during adipogenic commitment. ADSCs were cultured for 21 days in the presence of a specific adipogenic differentiation medium, together with metformin, or vitamin D, or both. We then analyzed the expression of FoxO1 and Heat Shock Proteins (HSP) and the secretion of proinflammatory cytokines IL-6 and TNF-α by ELISA. Autophagy was also assessed by specific Western blot analysis of ATG12, LC3B I, and LC3B II expression. Our results showed the ability of the conditioned media to modulate adipogenic differentiation, finely tuning the inflammatory response and autophagy. We observed a modulation in HSP mRNA levels, and a significant downregulation in cytokine secretion. Taken together, our findings suggest the possible application of these molecules in clinical practice to counteract uncontrolled lipogenesis and prevent obesity and obesity-related metabolic disorders.

scholarly journals Paeonia lactiflora Root Extract and Its Components Reduce Biomarkers of Early Atherosclerosis via Anti-Inflammatory and Antioxidant Effects In Vitro and In Vivo

Antioxidants ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1507
Author(s):  
Min Jeong Kim ◽  
Hyun-Hee Kang ◽  
Yeung Jin Seo ◽  
Kyung-Min Kim ◽  
Young-Jun Kim ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Quantitative Polymerase Chain Reaction ◽  
Root Extract ◽  
Methyl Gallate ◽  
Paeonia Lactiflora ◽  
Tnf Α ◽  
Antioxidant Effects ◽  
Early Atherosclerosis

Although various physiological activities of compounds obtained from Paeonia lactiflora have been reported, the effects of P. lactiflora extract (PLE) on early atherosclerosis remain unclear. Therefore, in this study, we investigated the in vitro and in vivo antiatherosclerosis and in vitro antioxidant effects of PLE and its compounds. PLE suppresses the tumor necrosis factor (TNF)-α-induced capacity of THP-1 cells to adhere to human umbilical vein endothelial cells (HUVECs), vascular cell adhesion molecule (VCAM)-1 expression, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in HUVECs. PLE also suppresses TNF-α-induced nuclear translocation of NF-κB p65 from cytosol as well as the enhanced TNFA and C-C motif chemokine ligand 2 (CCL2) mRNA expression in HUVECs. We identified and quantified the following PLE compounds using high-performance liquid chromatography with diode array detection: methyl gallate, oxypaeoniflorin, catechin, albiflorin, paeoniflorin, benzoic acid, benzoylpaeoniflorin, and paeonol. Among these, methyl gallate had the strongest inhibitory effect on monocyte adherence to TNF-α-induced HUVECs and the VCAM-1 expression. Reverse transcriptase real-time quantitative polymerase chain reaction showed that PLE compounds had a dissimilar inhibition effect on TNF-α-induced mRNA expression levels of CCL2, TNFA, and IL6 in HUVECs. Except for paeonol, the compounds inhibited lipopolysaccharide (LPS)-induced reactive oxygen species production in RAW264.7 cells. In vivo, oral administration of PLE improved TNF-α-induced macrophage infiltration to the vascular endothelium and expression of VCAM-1, as well as IL6 and TNFA gene expression in the main artery of mice. PLE could be useful as a nutraceutical material against early atherosclerosis via the combined effects of its components.

scholarly journals Nitro-oleic acid protects against endotoxin-induced endotoxemia and multiorgan injury in mice

2010 ◽  
Vol 298 (3) ◽  
pp. F754-F762 ◽  
Author(s):  
Haiping Wang ◽  
Haiying Liu ◽  
Zhunjun Jia ◽  
Curtis Olsen ◽  
Sheldon Litwin ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Mrna Expression ◽  
Plasma Urea ◽  
Monocyte Chemoattractant Protein 1 ◽  
Multiorgan Dysfunction ◽  
Reduced Ejection Fraction ◽  
Tnf Α ◽  
Anti Inflammatory

Nitroalkene derivatives of nitro-oleic acid (OA-NO2 ) are endogenous lipid products with potent anti-inflammatory properties in vitro. The present study was undertaken to evaluate the in vivo anti-inflammatory effect of OA-NO2 in mice given LPS. Two days before LPS administration, C57BL/6J mice were chronically infused with vehicle (LPS vehicle) or OA-NO2 (LPS OA-NO2) at 200 μg·kg−1·day−1 via osmotic minipumps; LPS was administered via a single intraperitoneal (ip) injection (10 mg/kg in saline). A third group received an ip injection of saline without LPS or OA-NO2 and served as controls. At 18 h of LPS administration, LPS vehicle mice displayed multiorgan dysfunction as evidenced by elevated plasma urea and creatinine (kidney), aspartate aminotransferase (AST) and alanine aminotransferase (ALT; liver), and lactate dehydrogenase (LDH) and reduced ejection fraction (heart). In contrast, the severity of multiorgan dysfunction was less in LPS OA-NO2 animals. The levels of circulating TNF-α and renal TNF-α mRNA expression, together with renal mRNA expression of monocyte chemoattractant protein-1, ICAM-1, and VCAM-1, and with renal mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase 2, and renal cGMP and PGE2 contents, were greater in LPS vehicle vs. control mice, but were attenuated in LPS OA-NO2 animals. Similar patterns of changes in the expression of inflammatory mediators were observed in the liver. Together, pretreatment with OA-NO2 ameliorated the inflammatory response and multiorgan injury in endotoxin-induced endotoxemia in mice.

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