scholarly journals Flunixin Meglumine Reduces Milk Isoprostane Concentrations in Holstein Dairy Cattle Suffering from Acute Coliform Mastitis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 834
Author(s):  
Carsten C. F. Walker ◽  
Jill L. Brester ◽  
Lorraine M. Sordillo
Keyword(s):  
Medical Intervention ◽  
Systemic Involvement ◽  
Analgesic Effects ◽  
Markers Of Inflammation ◽  
Inflammatory Mediator Production ◽  
Flunixin Meglumine ◽  
Coliform Mastitis ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxidant Status

Dysfunctional inflammation contributes significantly to the pathogenesis of coliform mastitis and the classical pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is the target of medical intervention using the non-steroidal anti-inflammatory drug (NSAID) flunixin meglumine (FM). Inhibition of COX-2 by FM can decrease concentrations of pro-inflammatory fatty acid-based mediators called eicosanoids, providing antipyretic and analgesic effects in dairy cows suffering from coliform mastitis. However, approximately 50% of naturally occurring coliform mastitis with systemic involvement results in death of the animal, even with NSAID treatment. Inadequate antioxidant potential (AOP) to neutralize reactive oxygen species (ROS) produced during excessive inflammation allows for oxidative stress (OS), contributing to tissue damage during coliform mastitis. Biomarkers of lipid peroxidation by ROS, called isoprostanes (IsoP), were used in humans and cattle to quantify the extent of OS. Blood IsoP were shown to be elevated and correlate with oxidant status during acute coliform mastitis. However, the effect of FM treatment on oxidant status and markers of OS has not been established. Blood IsoP concentrations were used to quantify systemic OS, whereas milk was used to assess local OS in the mammary gland. Results indicate that FM treatment had no effect on blood markers of inflammation but reduced the oxidant status index (OSi) by increasing blood AOP from pre- to post-FM treatment. Milk AOP significantly increased from pre- to post-FM treatment, whereas ROS decreased, resulting in a decreased OSi from pre- to post-FM treatment. The only blood IsoP concentration that was significantly different was 5-iso-iPF2α-VI, with a decreased concentration from pre- to post-FM treatment. Conversely, milk 5-iso-iPF2α-VI, 8,12-iso-iPF2α-VI, and total IsoP concentrations were decreased following FM treatment. These results indicated that administration of FM did improve systemic and local oxidant status and reduced local markers of OS. However, differential effects were observed between those animals that survived the infection and those that died, indicating that pre-existing inflammation and oxidant status greatly affect efficacy of FM and may be the key to reducing severity and mortality associated with acute coliform infections. Supplementation to improve AOP and anti-inflammatory mediator production may significantly improve efficacy of FM treatment.

scholarly journals Attenuation of inflammatory mediator production by the NF-κB member RelB is mediated by microRNA-146a in lung fibroblasts

2013 ◽  
Vol 304 (11) ◽  
pp. L774-L781 ◽  
Author(s):  
David H. McMillan ◽  
Collynn F. Woeller ◽  
Thomas H. Thatcher ◽  
Sherry L. Spinelli ◽  
Sanjay B. Maggirwar ◽  
...  
Keyword(s):  
Lung Inflammation ◽  
Inflammatory Mediator ◽  
Human Lung ◽  
Inflammatory Responses ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts ◽  
Small Noncoding Rnas ◽  
Inflammatory Mediator Production ◽  
Cox 2 ◽  
Anti Inflammatory

Lung inflammation can result from exposure to multiple types of inflammatory stimuli. Fibroblasts, key structural cells in the lung that are integral to inflammation and wound healing, produce inflammatory mediators after exposure to stimuli such as IL-1β. We and others have shown that the NF-κB member RelB has anti-inflammatory properties in mice. Little is known, however, about the anti-inflammatory role of RelB in human cells and how it functions. MicroRNAs (miRNAs), a novel class of small, noncoding RNAs, can mediate inflammatory signaling pathways, including NF-κB, through regulation of target gene expression. Our goal was to analyze the anti-inflammatory properties of RelB in human lung fibroblasts. We hypothesized that RelB regulates inflammatory mediator production in lung fibroblasts in part through a mechanism involving miRNAs. To accomplish this, we transfected human lung fibroblasts with a plasmid encoding RelB and small interfering (si)RNA targeting RelB mRNA to overexpress and downregulate RelB, respectively. IL-1β, a powerful proinflammatory stimulus, was used to induce NF-κB-driven inflammatory responses. RelB overexpression reduced IL-1β-induced cyclooxygenase (Cox)-2, PGE2, and cytokine production, and RelB downregulation increased Cox-2 expression and PGE2 production. Furthermore, RelB overexpression increased IL-1β-induced expression of miRNA-146a, an NF-κB-dependent miRNA with anti-inflammatory properties, whereas RelB downregulation reduced miRNA-146a. miR-146a overexpression ablated the effects of RelB downregulation on IL-1β-induced Cox-2, PGE2, and IL-6 production, suggesting that RelB mediates IL-1β-induced inflammatory mediator production in lung fibroblasts through miRNA-146a. RelB and miRNA-146a may therefore be new therapeutic targets in the treatment of lung inflammation caused by various agents and conditions.

Synthesis and Docking study of some bioactive N-(benzo[d]thiazol-2-yl)-2- (4-((substituted)phenoxy)acetamide on Cyclo-oxygenase-2 enzyme and invivo analgesic activity evaluation

2020 ◽  
Vol 17 ◽  
Author(s):  
Sumit Kumar ◽  
Arvind Kumar ◽  
Amit Verma ◽  
Arun Kumar Mishra
Keyword(s):  
Biological Activity ◽  
Catalytic Amount ◽  
Docking Study ◽  
Analgesic Effects ◽  
Benzothiazole Derivatives ◽  
Commercially Important ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Pharmacologically Active ◽  
Cox 2 Inhibitors

Background:: The benzothiazole and its derivatives reported an extremely key duty in the progress of commercially important intermediary molecules, which are wanted for the manufacture of various pharmacologically active agents. Introduction:: As a necessary element of ongoing examination for the synthesis of new Nonsteroidal anti-inflammatory agents (NSAIDs), a number of new benzothiazole derivatives were taken under thought for synthesis and were computationally studied along with biological activity. Methods:: Obtainable benzothiazole derivatives were synthesized by the condensing of 2-(4-aminophenoxy)-N- (benzo[d]thiazol-2-yl)acetamide with substituted acetophenones in ethanol in the presence of catalytic amount of glacial acetic acid. The structures of newly synthesized compounds were characterized by IR, NMR spectroscopy and elemental analysis techniques. Several molecular properties of these derivatives were computed in order to estimate their drug like candidates. Molecular docking was performed to these synthesized derivatives with particular reference to cyclooxygenase- 2 (COX-2) enzyme. The synthesized derivatives were screened for their biological activity, including analgesic and antiinflammatory activity as COX-2 inhibitors. Results and Discussion:: From all data, it established that among all target compounds, S-4 (N-(benzo[d]thiazol-2-yl)-2-(4- ((1-(3-nitrophenyl)ethylidene)amino) phenoxy)acetamide) displayed the highest anti-inflammatory and analgesic effects. Conclusion:: All these findings recommended that S-4 might be utilized as a promising new lead compound for Nonsteroidal anti-inflammatory drug (NSAIDs) development.

scholarly journals Mechanisms of Nonsteroidal Anti-Inflammatory Drug-Induced Gastrointestinal Injury and Repair: A Window of Opportunity for Cyclooxygenase-Inhibiting Nitric Oxide Donors

2004 ◽  
Vol 18 (4) ◽  
pp. 229-236 ◽  
Author(s):  
Rafael Perini ◽  
Stefano Fiorucci ◽  
John L Wallace
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Ulcer Healing ◽  
Significant Risk ◽  
Nitric Oxide Donors ◽  
Drug Induced ◽  
Analgesic Effects ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Cox 2 Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) cause damage in the upper gastrointestinal (GI) tract by impairing the ability of the mucosa to resist and respond to injury. Many of these effects of NSAIDs can be attributed to their ability to suppress mucosal prostaglandin synthesis. Selective inhibitors of cyclooxygenase (COX)-2 are less likely to disrupt mucosal defence and do not interfere with platelet aggregation. Thus, their use is associated with a reduced incidence of serious GI adverse events; however, a significant risk of such events still persists. At least in animal models, selective COX-2 inhibitors interfere with ulcer healing to the same extent as conventional NSAIDs. In contrast, COX-inhibiting nitric oxide donors (CINODs) produce anti-inflammatory and analgesic effects comparable or superior to those of NSAIDs, but with greatly reduced GI toxicity. Unlike NSAIDs and selective COX-2 inhibitors, CINODs do not interfere with ulcer healing. Moreover, because CINODs suppress the activity of both COX-1 and COX-2, they do not share with selective COX-2 inhibitors the lack of cardioprotection afforded by significant suppression of platelet aggregation. Because of their safety profile, CINODs may be particularly useful for long term prevention applications, such as for colon cancer, cardiovascular disease and Alzheimer's disease.

scholarly journals Ameliorative Effects of Scopoletin fromCrossostephium chinensisagainst Inflammation Pain and Its Mechanisms in Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Tien-Ning Chang ◽  
Jeng-Shyan Deng ◽  
Yi-Chih Chang ◽  
Chao-Ying Lee ◽  
Liao Jung-Chun ◽  
...  
Keyword(s):  
Tumor Necrosis ◽  
Formalin Test ◽  
Late Phase ◽  
No Synthase ◽  
Paw Edema ◽  
Analgesic Effects ◽  
Anti Oxidant ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Necrosis Factor

Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti-inflammatory activities reagent. In this study, we have investigated the analgesic effects of the scopoletin using the models of acetic acid-induced writhing response and the formalin test, the anti-inflammatory effects of scopoletin using model ofλ-carrageenan (Carr)-induced paw edema. The treatment of ICR mice with scopoletin inhibited the numbers of writhing response and the formalin-induced pain in the late phase. This study demonstrated that the administration of scopoletin resulted in the reduction of Carr-induced mice edema, and it increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) after Carr injection. We also demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level in the edema paw after Carr injection. Scopoletin decreased the NO, tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE2) levels on serum after Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti-inflammatory mechanisms of scopoletin might be related to the decrease in the level of MDAviaincreasing the activities of SOD, CAT, and GPx in the edema paw. Also, scopoletin could affect the production of NO, TNF-α, and PGE2, and therefore affect the anti-inflammatory effects.

Inhibition of LPS-Induced iNOS, COX-2 and Inflammatory Mediator Expression by Paeonol through the MAPKs Inactivation in RAW 264.7 Cells

2009 ◽  
Vol 37 (01) ◽  
pp. 181-194 ◽  
Author(s):  
Hee-Sung Chae ◽  
Ok-Hwa Kang ◽  
Young-Seob Lee ◽  
Jang-Gi Choi ◽  
You-Chang Oh ◽  
...  
Keyword(s):  
Inflammatory Mediator ◽  
Raw 264.7 Cells ◽  
Erk Activation ◽  
Analgesic Effects ◽  
A Cell ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Analgesic Activities ◽  
Biting Time

We evaluated the in vivo anti-inflammatory and analgesic activities of orally administered paeonol in mice, and also investigated the anti-inflammatory activity of paeonol in a cell line. Paeonol significantly reduced the edema induced by arachidonic acid in rats. The analgesic effects were assayed using 2 different models, i.e., by acetic acid-induced writhing response and by formalin induced licking and biting time. Moreover, we examined the effects of paeonol on the release of inflammatory mediators such as NO , PGE2 and IL-6. Our results demonstrated that paeonol inhibited LPS induced expression of NO , PGE2 and IL-6. Paeonol prevented LPS induced iNOS, COX-2 and ERK activation. Therefore, paeonol appears to have potential as a treatment for inflammatory disease and analgesic.

scholarly journals Cyclooxygenase-2 Inhibitory Compounds from the Leaves of Glycosmis pentaphylla (Retz.) A. DC.: Chemical and in silico Studies

2019 ◽  
Vol 31 (6) ◽  
pp. 1260-1264
Author(s):  
MAHFUZA AFROZ SOMA ◽  
MOHAMMAD FIROZ KHAN ◽  
FAIZA TAHIA ◽  
MD. ABDULLAH AL-MANSUR ◽  
MOHAMMAD SHARIFUR RAHMAN ◽  
...  
Keyword(s):  
In Silico ◽  
Spectroscopic Studies ◽  
Docking Studies ◽  
Phytochemical Analysis ◽  
In Silico Docking ◽  
Analgesic Effects ◽  
Inhibitory Compounds ◽  
In Silico Studies ◽  
Cox 2 ◽  
Anti Inflammatory

Glycosmis pentaphylla is traditionally used for treating many diseases in Bangladesh. Anti-inflammatory and analgesic effects of Glycosmis pentaphylla have been reported prominently but no bioactive element has been identified so far. In order to explore its analgesic and antiinflammatory compound(s), phytochemical analysis was conducted. Nine compounds were isolated from the methanol extract of leaves of Glycosmis pentaphylla whose structures were solved as arborinine (1), vanillic acid (2), 3-hydroxy-4-methoxybenzoic acid (3), benzoic acid (4), p-hydroxybenzoic acid (5), stigmasterol (6), β-amyrin (7), phytol (8) and 3α,16α-dihydroxyolean-12-ene (9) by spectroscopic studies, including high field 1H NMR analyses as well as co-TLC with authentic samples whenever possible. Among these, compounds 3 and 9 are the first report of their occurrence from G. pentaphylla. in silico docking studies of these metabolites with cyclooxygenase (COX)-2, an enzyme responsible for producing prostaglandins, were conducted. It was found that only arborinine and phytol can bind in the active site of COX-2, which might be considered as the major responsible moieties to cause analgesic and anti-inflammatory activities.

Cyclooxygenase isoforms and atherosclerosis

2003 ◽  
Vol 5 (9) ◽  
pp. 1-18 ◽  
Author(s):  
Orina Belton ◽  
Desmond J. Fitzgerald
Keyword(s):  
Side Effects ◽  
Chronic Administration ◽  
Selective Inhibition ◽  
Gastric Ulcers ◽  
Analgesic Effects ◽  
Vascular Regulation ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Effective Use ◽  
Cox 1

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist – COX-1 and COX-2 – both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by ‘coxibs’ (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.

scholarly journals Non-steroidal anti-inflammatory drugs: an overview

2019 ◽  
Vol 9 (1-s) ◽  
pp. 442-448 ◽  
Author(s):  
Kasturi Jahnavi ◽  
Palla Pavani Reddy ◽  
Bakshi Vasudha ◽  
Boggula Narender
Keyword(s):  
Side Effects ◽  
Gastrointestinal Haemorrhage ◽  
Cyclooxygenase Inhibitors ◽  
Full Spectrum ◽  
Analgesic Effects ◽  
Inflammatory Drugs ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Musculoskeletal Trauma ◽  
Cox 2 Inhibitors

Non-steroidal anti-inflammatory drugs (NSAIDs) including both traditional non-selective NSAIDs and the selective cyclooxygenase (COX)-2 inhibitors, are widely used for their anti-inflammatory and analgesic effects. NSAIDs are a necessary choice in pain management because of the integrated role of the COX path way in the generation of inflammation and in the biochemical recognition of pain. NSAIDs are the competitive inhibitors of cyclooxygenase (COX), the enzyme which mediates the bioconversion of arachidonic acid to inflammatory prostaglandins (PGs). Their use is associated with the side effects such as gastrointestinal and renal toxicity. They are the most commonly employed first line drugs for all these conditions and many others-like musculoskeletal trauma, minor aches and pains, and dysmenorrhoea. The therapeutic anti-inflammatory action of NSAIDs is produced by the inhibition of COX-2, while the undesired side effects arise from inhibition of COX-1 activity. Thus, it was though those more selective COX-2 inhibitors would have reduced side effects. Based upon a number of selective COX-2 inhibitors (Rofecoxib, Celecoxib etc.) were developed as safer NSAIDs with improved gastric safety profile. Several newer applications like prophylaxis of stroke with aspirin are now common place. Use of these drugs for the prophylaxis of conditions like Alzheimer’s disease and colorectal cancer is being evaluated. Unfortunately, they have several toxicities ranging from minor heartburn to severe gastrointestinal haemorrhage and perforation. Therefore, newer NSAIDs have been introduced in recent years to circumvent this problem. In preliminary studies, these have shown better safety, efficacy, and tolerability but the full spectrum of adverse reactions of these drugs is yet to be fully known. This review can be used for further research as well as clinical purpose. Keywords: Non-steroidal anti-inflammatory drugs (NSAIDs), cyclooxygenase inhibitors, prostaglandins, aspirin.

scholarly journals Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration

2021 ◽  
Vol 41 ◽  
Author(s):  
Paula A. Di Filippo ◽  
Francielli P. Gobbi ◽  
Gabriela B. Lemos ◽  
Célia R. Quirino ◽  
Carla B. Martins ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Proteins ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Clinical Signs ◽  
Standing Position ◽  
Surgical Trauma ◽  
Markers Of Inflammation ◽  
Flunixin Meglumine ◽  
Anti Inflammatory

ABSTRACT: Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p<0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and α1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.

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