scholarly journals Longer-Term Omega-3 LCPUFA More Effective Adjunct Therapy for Tuberculosis Than Ibuprofen in a C3HeB/FeJ Tuberculosis Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Frank E. A. Hayford ◽  
Mumin Ozturk ◽  
Robin C. Dolman ◽  
Renee Blaauw ◽  
Arista Nienaber ◽  
...  

Advancement in the understanding of inflammation regulation during tuberculosis (TB) treatment has led to novel therapeutic approaches being proposed. The use of immune mediators like anti-inflammatory and pro-resolving molecules for such, merits attention. Drug repurposing is a widely used strategy that seeks to identify new targets to treat or manage diseases. The widely explored nonsteroidal anti-inflammatory drug (NSAID) ibuprofen and a more recently explored pharmaconutrition therapy using omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs), have the potential to modulate the immune system and are thus considered potential repurposed drugs in this context. These approaches may be beneficial as supportive therapy to the already existing treatment regimen to improve clinical outcomes. Here, we applied adjunct ibuprofen and n-3 LCPUFA therapy, respectively, with standard anti-TB treatment, in a C3HeB/FeJ murine model of TB. Bacterial loads, lung pathology, lung cytokines/chemokines and lung lipid mediators were measured as outcomes. Lung bacterial load on day 14 post-treatment (PT) was lower in the n-3 LCPUFA, compared to the ibuprofen group (p = 0.039), but was higher in the ibuprofen group than the treated control group (p = 0.0315). Treated control and ibuprofen groups had more free alveolar space initially as compared to the n-3 LCPUFA group (4 days PT, p= 0.0114 and p= 0.002, respectively); however, significantly more alveolar space was present in the n-3 LCPUFA group as compared to the ibuprofen group by end of treatment (14 days PT, p = 0.035). Interleukin 6 (IL-6) was lower in the ibuprofen group as compared to the treated control, EPA/DHA and untreated control groups at 4 days PT (p = 0.019, p = 0.019 and p = 0.002, respectively). Importantly, pro-resolving EPA derived 9-HEPE, 11-HEPE, 12-HEPE and 18-HEPE lipid mediators (LMs) were significantly higher in the EPA/DHA group as compared to the ibuprofen and treated control groups. This suggests that n-3 LCPUFAs do improve pro-resolving and anti-inflammatory properties in TB, and it may be safe and effective to co-administer as adjunct therapy with standard TB treatment, particularly longer-term. Also, our results show host benefits upon short-term co-administration of ibuprofen, but not throughout the entire TB treatment course.

Author(s):  
Adeoye Joshua Oyewusi ◽  
Olayinka Ayotunde Oridupa ◽  
Adebowale Bernard Saba ◽  
Ibironke Kofoworola Oyewusi ◽  
Jonny Olufemi Olukunle

Abstract Objectives Several cultivars of Allium cepa L. have been studied for anti-inflammatory and analgesic activities but there is inadequate information on such biological activities of the concentrated extracts of the Nigerian grown red cultivar A. cepa bulb. Methods The anti-inflammatory models used in this study were Carrageenan-induced paw oedema and formalin-induced paw lick in rats, while acetic acid-induced abdominal writhing, hot plate reaction, hot water tail flick tests in mice were the analgesic models. Results At 30 min post-induction (pi), the inhibition of paw oedema (62.50%) by 200 mg/kg of methanol extract of red cultivar A. cepa bulb (MERCACB) was significantly (p<0.001) higher than that of indomethacin (15.63%) at 10 mg/kg. The paw oedema inhibition at 60 min pi by MERCACB (76.92%) was significantly higher than that of indomethacin (41.03%). At the early phase of formalin paw-lick test, the pain reaction time (PRT) of rat treated with MERCACB (400 mg/kg) was significantly lower than that of indomethacin and the control groups. The hotplate test revealed that PRT of mice treated with 800 mg/kg of MERCACB were significantly (p<0.01) longer in comparism to indomethacin and control groups. The PRT of mice subjected to thermal pain due to hot water and treated with 800 mg/kg of MERCACB was significantly (p<0.05) longer than that of the control group. Conclusions These findings indicate that MERCACB possesses potent anti-inflammatory and analgesic properties which confirm the traditional use of the plant for the treatment of inflammatory diseases and may be useful as a future therapeutic agent.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Thomas Köhnke ◽  
Beate Gomolka ◽  
Süleyman Bilal ◽  
Xiangzhi Zhou ◽  
Yanping Sun ◽  
...  

The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore,in vitroexperiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation.


Author(s):  
Ana Khusnul Faizah ◽  
Angelica Kresnamurti

Marine omega-3 from fish contains high EPA dan DHA which may have an analgesic and anti-inflammatory effects. The objective of study is to analyze the anti-inflammatory effect of marine omega-3 in rats. The method of this study is pre-post control experimental. The acute anti-inflammatory effect of marine omega-3 were investigated through carrageenan induced paw edema in rats. Thirty minutes before the procedure, the experimental groups were treated with fish oil 40 and 60 mg/kg; sodium diclofenac (5 mg/kg) as positive control groups and span 80-tween 80 as negative control groups. The degree of paw edema was measured by caliper. The marine omega-3 showed anti-inflammatory effect in a dose-dependent manner. The results of 60 mg/kg of marine omega-3 was significantly different compared with the negative. Overall, the marine omega-3 has acute anti-inflammatory activity in rats.


2021 ◽  
pp. 1-12
Author(s):  
John J. Feldmeier ◽  
◽  
John P. Kirby ◽  
Jay C. Buckey ◽  
Daphne W. Denham ◽  
...  

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world’s population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.


2021 ◽  
Vol 11 (3) ◽  
pp. 92
Author(s):  
Percy A Rojas ◽  
Olga S Timoteo ◽  
Teresa V Barreto ◽  
Zayra N Vila ◽  
Maxy B De Los Santos ◽  
...  

Background: Obesity is characterized by excessive accumulation of adipose tissue and is associated with higher risk of metabolic diseases and other comorbidities. Efficacious strategies including a diet high in “functional foods” are promising. Plukenetia huayllabambana known as Sacha Inchi (SI), is a legume which seeds are rich in proteins, tocopherols, and fatty acids such as omega-3 (ω-3). The latter has emerged as a potential protective nutrient against the cardiometabolic risks associated with obesity. Omega-3 changes the membrane lipid profile of hepatic and adipose cells triggering the expression of antioxidant and anti-inflammatory genes. However, there are few reports in relation to the effect of these oils in inflammatory and stress response related to obesity. In this sense, the present study evaluated the effect of SI oil emulsion on nitric oxide and leptin levels in the liver and some markers of oxidative stress and inflammation in adipose tissue from the rodent obesity model.Methods: Six groups were formed: Not obese control group (Noc), obese control (Oc), two groups treated with the emulsion of SI oil (Os1:0.25g ω-3/day; Os2:0.5g ω-3/day), one obese group treated with atorvastatin (Oa) and one group treated with atorvastatin plus the emulsion of SI oil (Oas2).Results: Os1 and Os2 lowered nitric oxide and increased liver leptin levels. In the adipose tissue, the superoxide dismutase and reducing antioxidant power increased significantly in Os1 and Os2 groups. The anti-inflammatory marker IL-4 wasalso increased in Os2, Oa and Oas2 compared to the Oc and IL-10 increased in Oas2 group.Conclusion: Our study suggests that the emulsion of SI oil can modify the inflammatory and stress responses associated with obesity and it can be incorporated as a promising functional food.Keywords: Inflammation, leptin, obesity, nitric oxide, oxidative stress, SI oil emulsion. 


2017 ◽  
Vol 7 (4) ◽  
pp. 291 ◽  
Author(s):  
Mohammed M. El-Seweidy ◽  
Sousou I. Ali ◽  
Sahar E. Elsweify ◽  
Abdelmoneim A. Ali ◽  
Mai M. Mashhour

Background: Osteoarthritis (OA) is a degenerative joint disease, characterized by abnormal remodeling pattern of joints driven by inflammatory mediators within the affected joints. Its symptoms are many like pain, stiffness, and decreased function.Objective:  The present study mainly focused on the anti-inflammatory effect of omega 3 fatty acids (F.As) versus diclofenac, non-steroidal anti-inflammatory drug in OA induced in ratsDesign: Intraarticular injection of monosodiumiodoacetate (MIA) 24.6 mg/kg in 0.6 ml saline was used to induce OA. Diclofenacand omega-3 F. These were administered orally, daily for 21 days and after 24 hours of OA induction.Results: Osteoarthritis induction resulted in an increase in serum levels of IL-6 (479.5%), TNF-a(545.5%), and CRP (754.2%) along with IL-10 level decrease (70.3%) as compared to normal group. Diclofenac intake demonstrated significant increase of IL-6 (24.9%), CRP (88.6%), and TNF-a (25.2%) compared to the OA control group. Omega 3 FAs intake showed significant reduction in inflammatory markers along with IL-10 increase, in comparison to OA group. Both treatment demonstrated a significant increase in TIMP2 along with decreased MMP2 and MPO in comparison with OA control. Positive correlation of IL-6 with MPO (r = 0.7, P=0.002), and negative one with IL-10 (r = 0.9, p<0.0001) and TIMP2 (r = -0.5, p<0.008) was observed. Interleukin-10 was negatively correlated with MMP2 (r = - 0.5, p<0.007) and MPO (r = -0.8, p<0.0001).Conclusion: Data derived from biochemical and histopathological results, indicated that omega3 FAs may be expressed as a natural anti-inflammatory agent of a significant potential in OA with evident remarkable effect.Keywords: OA; omega3FAs; diclofenac; MMP2; TIMP2; MPO


Author(s):  
Adele Bahar ◽  
Ozra Akha ◽  
Mahdi Bordbar ◽  
Saeid Abediankenari ◽  
Rezaali Mohammadpoor ◽  
...  

Introduction: Inflammatory state is considered as the pathogenesis of Gestational Diabetes Mellitus (GDM). Cytokines can cause insulin resistance and maybe the molecular basis of inflammation in Diabetes Mellitus (DM). Aim: To assess the level of Interleukin-10 (IL-10) in addition to a new anti-inflammatory cytokine marker Interleukin-35 (IL-35) in pregnant women with and without GDM. Materials and Methods: Participants in the study included 29 pregnant women with GDM (case group) and 29 healthy pregnant women (control group). Blood levels of IL-10, IL-35, Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP) were measured in all participants. Independent t-test and Chi-square test were used for data analysis. Quantitative data between three gestational subgroups (<29, 29-32 and >32 weeks) in each GDM and control group were compared by ANOVA test. The p-value <0.05 was considered significant. Results: The mean levels of IL-10 were 1.03±0.85 and 0.83±0.57 pg/mL (p=0.284) and the mean IL-35 concentrations were 10.2±8.1 and 8.8±4.3 pg/mL (p=0.437) in GDM and control groups, respectively. The mean CRP and ESR levels were higher in the GDM group than the controls but the differences were not statistically significant. In the GDM group, IL-10 was significantly lower at the early stage of pregnancy (<29 weeks) compared to the later stage (>32 weeks) (p=0.04), but this was not true in the control group. There was no significant difference between the mean level of IL-35 at different gestational ages in both GDM and control groups. Conclusion: The present study showed the decreased level of anti-inflammatory marker IL-10 in the late stage of pregnancy in diabetic women especially during the last weeks of gestation. New inflammatory marker IL-35 was not statistically significant in GDM subjects.


2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Shahida A. Khan ◽  
Ashraf Ali ◽  
Sarah A. Khan ◽  
Solafa A. Zahran ◽  
Ghazi Damanhouri ◽  
...  

Obesity today stands at the intersection between inflammation and metabolic disorders causing an aberration of immune activity, and resulting in increased risk for diabetes, atherosclerosis, fatty liver, and pulmonary inflammation to name a few. Increases in mortality and morbidity in obesity related inflammation have initiated studies to explore different lipid mediated molecular pathways of attempting resolution that uncover newer therapeutic opportunities of anti-inflammatory components. Majorly the thromboxanes, prostaglandins, leukotrienes, lipoxins, and so forth form the group of lipid mediators influencing inflammation. Of special mention are the omega-6 and omega-3 fatty acids that regulate inflammatory mediators of interest in hepatocytes and adipocytes via the cyclooxygenase and lipoxygenase pathways. They also exhibit profound effects on eicosanoid production. The inflammatory cyclooxygenase pathway arising from arachidonic acid is a critical step in the progression of inflammatory responses. New oxygenated products of omega-3 metabolism, namely, resolvins and protectins, behave as endogenous mediators exhibiting powerful anti-inflammatory and immune-regulatory actions via the peroxisome proliferator-activated receptors (PPARs) and G protein coupled receptors (GPCRs). In this review we attempt to discuss the complex pathways and links between obesity and inflammation particularly in relation to different lipid mediators.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1350.3-1350
Author(s):  
S. Perniola ◽  
S. Alivernini ◽  
B. Tolusso ◽  
M. R. Gigante ◽  
M. Gessi ◽  
...  

Background:The regulation of inflammation is a dynamic process involving several molecules as lipid mediators. The Specialized Pro-resolving Mediators (SPMs), such as Resolvin (RvD and RvE), Protectins, Maresins and Lipoxin A4 (LXA4), are bioactive metabolites of omega-3 and omega-6 fatty acids which drive inflammatory resolution phase and promote tissue repair. ERV, ALX/FPR2 and BLT1 are SPM receptors. Although in Rheumatoid Arthritis (RA) lipid mediators role within pathophysiology is under definition, studies on SPMs receptors role are still lacking in this disease.Objectives:Purpose of this study is to define ERV, ALX/FPR2 and BLT1 expression in blood derived leukocytes and synovial cells and to correlate it to disease activity to define SPM receptors ad inflammatory resolution biomarkers in RA patients.Methods:A cohort of 52 RA patients was enrolled in the study of which 40 with active disease (DAS28= 5,35 (5,18-6,40)) and 12 in sustained remission status (DAS28= 2,1 (1,83-2,42)). Each enrolled patient underwent peripheral blood (PB) drawing and 46 of them underwent US-guided synovial tissue (ST) biopsy. FACS gating strategy was used for PB and ST processing to evaluate percentage of positive cells and the mean fluorescence intensity (MFI) of ERV+, ALX/FPR2+and BLT1+in CD45+CD3+, CD45+CD19+for PB and ST, CD45+CD14+and neutrophils for PB only and CD45-CD90+, CD45+CD64+CD11b+macrophages (distinct in CD206+and CD206-subpopulations) for ST only. Each included ST was stained with haematoxylin/eosin and categorized by a pathologist, blinded to clinical characteristics, using the Krenn Score (KS) to assess ST inflammation degree. As control group, 11 undifferentiated peripheral inflammatory arthritis (UPIA) patients were enrolled in the study.Results:Considering the whole RA cohort, DAS28 inversely correlated with BLT1+positive cells on ST-derived CD45+(r= -0.48; p= 0.048), CD3+(r= -0.56; p= 0.019) and CD19+(r= -0.49; p= 0.042) cells, in contrast with CD90+(r= 0.50; p= 0.041) cells. Similarly, both DAS28 and KS inversely correlated with ALX/FPR2+positive cells in ST-derived CD45+(r= -0.42, p= 0.050 and r= -0,41, p= 0,046 respectively) cells. Evaluating the MFI levels of the SPM receptors along all RA stages (naïve-to-treatment, resistant-to-treatment, sustained remission) compared with UPIA control group, interestingly ST-derived CD45+cells of remission RA were depleted of ERV1 compared to naïve-to-treatment RA (p=0.04), despite comparable ST inflammation. Furthermore, highest ERV1 expression was found in ST-derived CD45+CD3+and CD45+CD19+cells in naïve-to-treatment RA compared with UPIA patients (p= 0,045 and p= 0,012 respectively). Moreover, the lowest BLT1 level was found in remission RA CD3+cells compared with UPIA and naïve-to-treatment RA patients (p= 0,008 and p= 0,023 respectively).Conclusion:SPM receptors expression seem to be tightly related to disease activity in the synovial tissue, suggesting an important involvement in the inflammatory process in RA patient.References:[1]Serhan CN. Nature, 2014.[2]Alivernini S, et al. Arthritis Res Ther 2016[3]Krenn V et al. Histopathology, 2006.Disclosure of Interests:Simone Perniola: None declared, Stefano Alivernini: None declared, Barbara Tolusso: None declared, Maria Rita Gigante: None declared, Marco Gessi: None declared, Clara Di Mario: None declared, Luca Petricca: None declared, Annunziata Capacci: None declared, Anna Laura Fedele: None declared, Gianfranco Ferraccioli: None declared, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB


Author(s):  
Noor D Aziz ◽  
Mazin H. Ouda ◽  
Moayad Mijbil Ubaid

Objective: Nonsteroidal anti-inflammatory drugs (NSAIDs) do not reverse the disease progression, but they provide relief from pain and inflammation by inhibiting cyclooxygenase (COX) enzymes mediating the inflammatory pathway. Our aim was to make a meaningful comparison of both selective and non-selective COX-2 inhibitor to evaluate their toxic effects by measuring biochemical and histological alterations of heart, liver, and kidney.Methods: This study was conducted on 18 Sprague-Dawley rats of both sexes for 30 days, rats were divided into three groups (control group, ibuprofen group, and celecoxib group) each group included six rats.Results: The results are revealed that serum level of alanine aminotransferase, aspartate aminotransferase, alkaline phosphates, and total serum bilirubin was significantly increased (p<0.05) in ibuprofen and celecoxib group when compared with control, the highest level in celecoxib group, also serum level of urea was significantly elevated (p<0.05) in ibuprofen group when compared with control and celecoxib groups. Histopathological changes in cardiac tissue represented by vascular congestion and pericardial infiltration which are more prominent in celecoxib group, the changes in liver tissue revealed by vascular congestion and mild portal tract inflammation which is chronic in celecoxib group, while histological alterations in kidney tissue represented by severe vascular congestion with tubular necrosis which is more prominent in ibuprofen group.Conclusion: Both ibuprofen and celecoxib group have toxic effects on heart, liver, and kidney represented by the biochemical and histopathological findings.


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