scholarly journals Neutrophil-Mediated Gastrointestinal Injury

1998 ◽  
Vol 12 (8) ◽  
pp. 559-568 ◽  
Author(s):  
Susan N Elliott ◽  
John L Wallace
Keyword(s):  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Host Tissue ◽  
Gastrointestinal Disorders ◽  
Beneficial Effects ◽  
Gastrointestinal Injury ◽  
Neutrophil Extravasation ◽  
Inflammatory Drugs ◽  
Significant Injury

Inflammatory diseases of the gastrointestinal tract are frequently characterized by a dense infiltration of neutrophils in the lamina propria and the subsequent transepithelial migration of these cells into the lumen. While the neutrophil plays an essential role in defending against bacterial infection, it can also cause significant injury to the host tissue. The evidence for a role of neutrophils in producing significant tissue injury in a number of gastrointestinal disorders and the mechanisms through which neutrophils produce tissue injury are reviewed. Furthermore, the evidence that some commonly used anti-inflammatory drugs produce beneficial effects through modulation of neutrophil extravasation or activation is reviewed.

scholarly journals Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

2021 ◽  
Vol 14 (7) ◽  
pp. 692
Author(s):  
Ryldene Marques Duarte da Cruz ◽  
Francisco Jaime Bezerra Mendonça-Junior ◽  
Natália Barbosa de Mélo ◽  
Luciana Scotti ◽  
Rodrigo Santos Aquino de Araújo ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Structural Characteristics ◽  
Tiaprofenic Acid ◽  
Inflammatory Activity ◽  
Drug Candidates ◽  
Biological Target ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Privileged Structures

Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

THE ROLE OF MYELOPEROXIDASE AND NEUTROPHIL EXTRACELLULAR TRAPS IN THE PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S4-S4
Author(s):  
Belal Chami ◽  
Gulfam Ahmad ◽  
Angie Schroder ◽  
Patrick San Gabriel ◽  
Paul Witting
Keyword(s):  
Disease Severity ◽  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Activity Index ◽  
Critical Role ◽  
Neutrophil Migration ◽  
Sodium Sulphate ◽  
Host Tissue ◽  
Neutrophil Extracellular Trap

Abstract Neutrophils are short-lived immune cells that represent the major cell type recruited to the inflamed bowel releasing their azurophilic granules containing enzymes myeloperoxidase (MPO). Fecal and serum MPO levels has previously been shown to correlate to disease severity in IBD patients. MPO, in the presence of H2O2 and free Cl- undergoes a halogenation cycle, yielding the two-electron oxidant, hypochlorous acid (HOCl) - a potent bactericidal agent. However, chronic intestinal exposure to MPO/HOCl due to perpetual inflammation may cause secondary host-tissue injury and cell death. Neutrophil Extracellular Trap (NET)osis is a specialised form of neutrophil death where MPO is entrapped in a DNA scaffold and continues to elicit HOCl activity and may further contribute to host-tissue injury. We investigated the presence of NETs in surgically excised ileum samples from CD and healthy patients using advanced confocal microscopic techniques and found MPO, Neutrophil Elastase (NE) and Citrullinated Histone h3 (CitH3) - critical components of NET formation, individually positively correlate to the severity of histopathological intestinal injury. Furthermore, multiplex Opal™ IHC performed using LMS880 Airyscan-moduled microscopy with z-stacking revealed colocalization of NE, MPO, CitH3 and DAPI indicating the extensive presence of NETs in severely affected CD tissue. Using two pharmacological inhibitors of MPO in a dextran sodium sulphate (DSS) model of murine colitis, we demonstrated the pathological role of MPO in experimental colitis. MPO inhibitors, TEMPOL and AZD3241 delivered via daily i.p significantly rescued the course of colitis by abrogating clinical indices including body weight loss, disease activity index, inhibiting serum peroxidation, and preserving colon length, while significantly mitigating histoarchitectural damage associated with DSS-induced colitis. We also showed that MPO inhibition decreased neutrophil migration to the gut, suggesting MPO may play a role in perpetuating the inflammatory cell by further recruiting cells to the inflamed gut. Collectively, we have shown for the first time that MPO is not only an important clinical marker of disease severity but may also play a critical role in perpetuating host-tissue damage and inflammation.

The role of celecoxib as a potential inhibitor in the treatment of inflammatory diseases - a review

2021 ◽  
Vol 28 ◽  
Author(s):  
Josiane Viana Cruz ◽  
Joaquín María Campos Rosa ◽  
Njogu Mark Kimani ◽  
Silvana Giuliatti ◽  
Cleydson Breno Rodrigues dos Santos
Keyword(s):  
Side Effects ◽  
Inflammatory Diseases ◽  
Structural Basis ◽  
Potential Inhibitor ◽  
Cyclooxygenase 1 ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

: This article presents a simplified view of celecoxib as a potential inhibitor in the treatment of inflammatory diseases. The enzyme cyclooxygenase (COX) has, predominantly, two isoforms called cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). The former plays a constitutive role that is related to homeostatic effects in renal and platelets, while the latter is mainly responsible for induction of inflammatory effects. Since COX-2 plays an important role in the pathogenesis of inflammatory diseases, it has been signaled as a target for the planning of anti-inflammatory intermediates. Many inhibitors developed and planned for COX-2 inhibition have presented side effects to humans, mainly in the gastrointestinal and/or cardiovascular tract. Therefore, it is necessary to design new potential COX-2 inhibitors, which are relatively safe and without side effects. To this end, of the generation of non-steroidal anti-inflammatory drugs from “coxibs”, celecoxib is the only potent selective COX-2 inhibitor that is still commercially available. Thus, the compound celecoxib became a commercial prototype inhibitor for the development of anti-inflammatory agents for COX-2 enzyme. In this review, we provide highlights where such inhibition should provide a structural basis for the design of promising new non-steroidal anti-inflammatory drugs (NSAIDs) which act as COX-2 inhibitors with lesser side effects on the human body.

V. Therapeutic potential of nitric oxide donors and inhibitors

1999 ◽  
Vol 276 (6) ◽  
pp. G1313-G1316 ◽  
Author(s):  
Marcelo N. Muscará ◽  
John L. Wallace
Keyword(s):  
Nitric Oxide ◽  
Therapeutic Potential ◽  
Tissue Injury ◽  
Mucosal Injury ◽  
Therapeutic Agents ◽  
Gastrointestinal Physiology ◽  
Inflammatory Drugs ◽  
Nitric Oxide Releasing ◽  
Oxide Synthase

Nitric oxide is a crucial mediator of gastrointestinal mucosal defense, but, paradoxically, it also contributes to mucosal injury in several situations. Inhibitors of nitric oxide synthesis and compounds that release nitric oxide have been useful pharmacological tools for evaluating the role of nitric oxide in gastrointestinal physiology and pathophysiology. Newer inhibitors with selectivity for one of the isoforms of nitric oxide synthase are even more powerful tools and may have utility as therapeutic agents. Also, agents that can scavenge nitric oxide or peroxynitrite are promising as drugs to prevent nitric oxide-associated tissue injury. Compounds that release nitric oxide in small amounts over a prolonged period of time may also be very useful for prevention of gastrointestinal injury associated with shock and with the use of drugs that have ulcerogenic effects. Indeed, the coupling of a nitric oxide-releasing moiety to nonsteroidal anti-inflammatory drugs has proven to be a valid means of substantially reducing the gastrointestinal toxicity of these drugs without decreasing their efficacy.

scholarly journals High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn- IgG complexes

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 184-193 ◽  
Author(s):  
HU Lutz ◽  
P Stammler ◽  
E Jelezarova ◽  
M Nater ◽  
PJ Spath
Keyword(s):  
Inflammatory Diseases ◽  
Factor H ◽  
Human Igg ◽  
Partial Protection ◽  
Beneficial Effects ◽  
High Concentrations ◽  
High Doses ◽  
Immune Aggregates

Abstract Intravenously applied human IgG has beneficial effects in treating inflammatory diseases, presumably because it has a complement attenuating role. This role of IgG was studied in vitro by following C3 activation and inactivation in sera that were supplemented with exogenous human IgG and incubated with immune aggregates. IgG added at 2 to 10 mg/mL stimulated the physiologic inactivation of C3b-containing complexes twofold to threefold in 20% sera. This, in turn, lowered the overall C3 activation by 28%, as new C3 convertases primarily assembled on C3b-containing complexes. Exogenous IgG (5 mg/mL) also stimulated inactivation of purified C3b2-IgG complexes, whereby their half-life dropped from 3–4 to 1.5 minutes in 20% serum. IgG appeared to act like a modulator of factor H and I because it did not stimulate inactivation of C3b-containing complexes in factor I-deficient serum. Thus, the known partial protection of C3bn-IgG complexes from inactivation by factor H and I was downregulated by high concentrations of IgG. The ability of high doses of IgG to stimulate complement inactivation is a novel regulatory role of IgG. This may be one of the molecular principles for its therapeutic efficacy in treating complement-mediated inflammations.

Mechanisms and pathophysiological implications of sinusoidal endothelial cell gap formation following treatment with galactosamine/endotoxin in mice

2006 ◽  
Vol 291 (2) ◽  
pp. G211-G218 ◽  
Author(s):  
Yoshiya Ito ◽  
Edward R. Abril ◽  
Nancy W. Bethea ◽  
Margaret K. McCuskey ◽  
Cathleen Cover ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Initial Contact ◽  
Gap Formation ◽  
Neutrophil Accumulation ◽  
Mmp Inhibitor ◽  
Phenyl Propionic Acid ◽  
Neutrophil Extravasation ◽  
Initial Appearance ◽  
Blood Elements

Neutrophil extravasation from sinusoids is a critical step for acute inflammatory tissue injury. However, the role of sinusoidal endothelial cells (SECs) in this process remains unclear. Matrix metalloproteinases (MMPs) have been shown to involve gap formation in SECs in several liver diseases. Therefore, the present study examined SEC modifications elicited by galactosamine (Gal)/endotoxin (ET). Treatment of male C3Heb/FeJ mice with Gal/ET or Gal/TNF caused the formation of numerous gaps in SECs at 4 h when no neutrophil extravasation occurred. Six hours after Gal/ET or Gal/TNF treatment, blood elements started to penetrate to the extrasinusoidal space through large gaps. Treatment with ET alone caused sinusoidal neutrophil accumulation but no gap formation, neutrophil extravasation, or hemorrhage. Gal/ET treatment increased hepatic MMP-2 and MMP-9 mRNA expression (6.7- and 11-fold, respectively). Pretreatment with 2-[(4-biphenylsulfonyl) amino]-3-phenyl-propionic acid, an MMP-2/MMP-9 inhibitor (5 mg/kg), minimized gap formation after Gal/ET and Gal/TNF treatment. The MMP inhibitor reduced injury only in the Gal/ET model mainly due to reduced TNF formation. The MMP inhibitor attenuated sinusoidal neutrophil accumulation at 6 h but failed to attenuate Gal/TNF-induced liver injury at 7 h due to excessive apoptosis. These results suggest that Gal/ET or Gal/TNF activates MMPs, which are responsible for SEC gap formation. Although the initial appearance of gap formation is independent of neutrophils, the gaps allow initial contact of neutrophils with damaged hepatocytes. In addition, MMP activation promotes neutrophil accumulation in sinusoids.

scholarly journals Evaluation of the Effects of Different Bacteroides vulgatus Strains against DSS-Induced Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Sijia Li ◽  
Chen Wang ◽  
Chengcheng Zhang ◽  
Yanhong Luo ◽  
Qianqian Cheng ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Activity Index ◽  
Genomic Analysis ◽  
Disease Activity Index ◽  
Short Chain Fatty Acids ◽  
Comparative Genomic ◽  
Necrosis Factor Alpha ◽  
Beneficial Effects ◽  
Underlying Causes

Although the strain-dependent effects of Bacteroides vulgatus on alleviating intestinal inflammatory diseases have been demonstrated, the literature has rarely focused on the underlying causes of this effect. In this study, we selected four B. vulgatus strains (FTJS5K1, FTJS7K1, FSDTA11B14, and FSDLZ51K1) with different genomic characteristics and evaluated their protective roles against dextran sulfate sodium- (DSS-) induced colitis. Compared to the other three tested strains, B. vulgatus 7K1 more strongly ameliorated the DSS-induced weight loss, shortening of the colon length, increased disease activity index scores, colonic tissue injury, and immunomodulatory disorder. In contrast, B. vulgatus 51K1 significantly worsened the DSS-induced alterations in the tumor necrosis factor-alpha (TNF-α) concentration and colonic histopathology. A comparative genomic analysis of B. vulgatus 7K1 and 51K1 showed that the beneficial effects of B. vulgatus 7K1 may be associated with some of its specific genes involved in the production of short-chain fatty acids or capsular polysaccharides and enhancement of its survivability in the gut. In conclusion, these findings indicate that the supplementation of B. vulgatus 7K1 is a potentially efficacious intervention for alleviating colitis and provides scientific support for the screening of probiotics with anticolitis effect.

scholarly journals Sulfonylureas for Treatment of Periodontitis-Diabetes Comorbidity-Related Complications: Killing Two Birds With One Stone

2021 ◽  
Vol 12 ◽  
Author(s):  
Luxi Yang ◽  
Qing Ge ◽  
Zhitong Ye ◽  
Lijing Wang ◽  
Liping Wang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Host Immune System ◽  
Bone Homeostasis ◽  
Vascular Growth ◽  
Beneficial Effects ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Oral Hypoglycemic Drugs ◽  
Sulfonylurea Drugs

Periodontitis is one of the most prevalent oral inflammatory diseases leading to teeth loss and oral health problems in adults. Periodontitis mainly affects periodontal tissue by affecting the host immune system and bone homeostasis. Moreover, periodontitis is associated with various systemic diseases. Diabetes is a metabolic disease with systemic effects. Both periodontitis and diabetes are common inflammatory diseases, and comorbidity of two diseases is linked to exacerbation of the pathophysiology of both diseases. Since bacterial dysbiosis is mainly responsible for periodontitis, antibiotics are widely used drugs to treat periodontitis in clinics. However, the outcomes of antibiotic treatments in periodontitis are not satisfactory. Therefore, the application of anti-inflammatory drugs in combination with antibiotics could be a treatment option for periodontitis-diabetes comorbidity. Anti-diabetic drugs usually have anti-inflammatory properties and have shown beneficial effects on periodontitis. Sulfonylureas, insulin secretagogues, are the earliest and most widely used oral hypoglycemic drugs used for type-2 diabetes. Studies have found that sulfonylurea drugs can play a certain role in the mitigation of periodontitis and inflammation. This article reviews the effects of sulfonylurea drugs on the mitigation of periodontitis-diabetes comorbidity-related inflammation, bone loss, and vascular growth as well as the involved molecular mechanisms. We discuss the possibility of a new application of sulfonylureas (old drug) to treat periodontitis-diabetes comorbidity.

scholarly journals Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Meerza Abdul Razak ◽  
Pathan Shajahan Begum ◽  
Buddolla Viswanath ◽  
Senthilkumar Rajagopal
Keyword(s):  
Amino Acid ◽  
Inflammatory Diseases ◽  
Well Being ◽  
Low Molecular Weight ◽  
Quality Of Sleep ◽  
Beneficial Effects ◽  
Disease States ◽  
Nonessential Amino Acid

Glycine is most important and simple, nonessential amino acid in humans, animals, and many mammals. Generally, glycine is synthesized from choline, serine, hydroxyproline, and threonine through interorgan metabolism in which kidneys and liver are the primarily involved. Generally in common feeding conditions, glycine is not sufficiently synthesized in humans, animals, and birds. Glycine acts as precursor for several key metabolites of low molecular weight such as creatine, glutathione, haem, purines, and porphyrins. Glycine is very effective in improving the health and supports the growth and well-being of humans and animals. There are overwhelming reports supporting the role of supplementary glycine in prevention of many diseases and disorders including cancer. Dietary supplementation of proper dose of glycine is effectual in treating metabolic disorders in patients with cardiovascular diseases, several inflammatory diseases, obesity, cancers, and diabetes. Glycine also has the property to enhance the quality of sleep and neurological functions. In this review we will focus on the metabolism of glycine in humans and animals and the recent findings and advances about the beneficial effects and protection of glycine in different disease states.

scholarly journals Role of in Asthma and Nonasthmatic Eosinophilic Bronchitis

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Beatriz Sastre ◽  
Victoria del Pozo
Keyword(s):  
Respiratory Diseases ◽  
Inflammatory Diseases ◽  
Direct Action ◽  
Airflow Obstruction ◽  
Eosinophilic Bronchitis ◽  
Beneficial Effects ◽  
Airway Function ◽  
Smooth Muscle Proliferation ◽  
The Difference

Eosinophilic bronchitis is a common cause of chronic cough, which like asthma is characterized by sputum eosinophilia, but unlike asthma there is no variable airflow obstruction or airway hyperresponsiveness. Several studies suggest that prostaglandins may play an important role in orchestrating interactions between different cells in several inflammatory diseases such as asthma. PGE2is important because of the multiplicity of its effects on immune response in respiratory diseases; however, respiratory system appears to be unique in that PGE2has beneficial effects. We described that the difference in airway function observed in patients with eosinophilic bronchitis and asthma could be due to differences in PGE2production. PGE2present in induced sputum supernatant from NAEB patients decreases BSMC proliferation, probably due to simultaneous stimulation of EP2 and EP4 receptors with inhibitory activity. This protective effect of PGE2may not only be the result of a direct action exerted on airway smooth-muscle proliferation but may also be attributable to the other anti-inflammatory actions.

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