ArticleBritish journal of pharmacology2008
Attenuation of inflammation and cytokine production in rat colitis by a novel selective inhibitor of leukotriene A4 hydrolase.
Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of animal models of post-infectious/post-inflammatory irritable bowel syndrome.Journal of gastroenterology · 2011Pooled it
- Ulcerative colitis: from molecular pathophysiology to management and the emerging role of natural and pharmacological drug candidates.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Article
- Article
- The Effects of Exercise Training and High Triglyceride Diet in an Estrogen Depleted Rat Model: The Role of the Heme Oxygenase System and Inflammatory Processes in Cardiovascular Risk.Journal of sports science & medicine · 2018Article
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- Production of lipid mediators across different disease stages of dextran sodium sulfate-induced colitis in mice.Journal of lipid research · 2018Article
- Myeloid Cell Hypoxia-Inducible Factors Promote Resolution of Inflammation in Experimental Colitis.Frontiers in immunology · 2018Article
- Feasibility and physiological relevance of designing highly potent aminopeptidase-sparing leukotriene A4 hydrolase inhibitors.Scientific reports · 2017Article
- Bathing effects of east saline groundwater concentrates on allergic (atopic) dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in hairless mice.Experimental and therapeutic medicine · 2017Article
- The development of novel LTAScientific reports · 2017Article
- Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen-Deficient Rat.Oxidative medicine and cellular longevity · 2017Article
- Differential Expression of Inflammation-Related Genes in Children with Down Syndrome.Mediators of inflammation · 2016Article
- Matrikines are key regulators in modulating the amplitude of lung inflammation in acute pulmonary infection.Nature communications · 2015Article
- Bathing Effects of Various Seawaters on Allergic (Atopic) Dermatitis-Like Skin Lesions Induced by 2,4-Dinitrochlorobenzene in Hairless Mice.Evidence-based complementary and alternative medicine : eCAM · 2015Article
- Schisandrae Fructus Supplementation Ameliorates Sciatic Neurectomy-Induced Muscle Atrophy in Mice.Oxidative medicine and cellular longevity · 2015Article
- Leukotrienes in pulmonary arterial hypertension.Immunologic research · 2014Review
- Effect of DHU001, a Polyherbal Formula on Formalin-induced Paw Chronic Inflammation of Mice.Toxicological research · 2011Article
- A critical role for LTA4H in limiting chronic pulmonary neutrophilic inflammation.Science (New York, N.Y.) · 2010Article
- The effects of Delta-tetrahydrocannabinol and cannabidiol alone and in combination on damage, inflammation and in vitro motility disturbances in rat colitis.British journal of pharmacology · 2010Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeLeukotriene B(4) (LTB(4)), formed by the sequential actions of the 5-lipoxygenase (5-LO) and leukotriene A(4) hydrolase (LTA(4)H), is a pro-inflammatory mediator implicated in the pathogenesis of inflammatory bowel disease. However, inhibitors of 5-LO have not proved to be consistent in their therapeutic efficacy in colitis. Another approach to inhibiting LTB(4) synthesis is through the use of inhibitors of LTA(4)H, such as the novel, potent and selective compound, JNJ 26993135. EXPERIMENTAL APPROACH: The effect of oral administration of JNJ 26993135 has been evaluated in a rat model of colitis provoked by colonic instillation of trinitrobenzenesulphonic acid (TNBS). The extent and severity of the macroscopic inflammatory response, the colonic levels of myeloperoxidase (MPO) and LTB(4) and of the pro-inflammatory cytokines, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were measured. KEY
resultsOral administration of JNJ 26993135 (5, 15 and 30 mg kg(-1), twice a day) dose-dependently reduced both the extent and intensity of the colonic inflammatory damage observed 3 days after TNBS challenge. JNJ 26993135 also dose-dependently reduced the elevated colonic levels of LTB(4), as well as the inflammatory biomarkers, MPO, IL-6 and TNF-alpha. This dosing regimen was supported by the pharmacokinetic profile of JNJ 26993135, along with the demonstration of the inhibition of ex vivo production of LTB(4) in whole blood following oral administration. CONCLUSIONS AND IMPLICATIONS: These results with JNJ 26993135 in the rat TNBS model support the role of LTB(4) in colitis and the potential value of targeting LTA(4)H for the treatment of inflammatory bowel diseases.
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