The universe of arachidonic acid metabolites in inflammatory bowel disease

AbstractThe aim of this study was to investigate the effects of the administration of oral arachidonic acid (AA) in rats with or without dextran sulphate sodium (DSS)-induced inflammatory bowel disease. Male Wistar rats were administered AA at 0, 5, 35 or 240 mg/kg daily by gavage for 8 weeks. Inflammatory bowel disease was induced by replacing drinking water with 3 % DSS solution during the last 7 d of the AA dosing period. These animals passed loose stools, diarrhoea and red-stained faeces. Cyclo-oxygenase-2 concentration and myeloperoxidase activity in the colonic tissue were significantly increased in the animals given AA at 240 mg/kg compared with the animals given AA at 0 mg/kg. Thromboxane B2 concentration in the medium of cultured colonic mucosae isolated from these groups was found to be dose-dependently increased by AA, and the increase was significant at 35 and 240 mg/kg. Leukotriene B4 concentration was also significantly increased and saturated at 5 mg/kg. In addition, AA at 240 mg/kg promoted DSS-induced colonic mucosal oedema with macrophage infiltration. In contrast, administration of AA for 8 weeks, even at 240 mg/kg, showed no effects on the normal rats. These results suggest that in rats with bowel disease AA metabolism is affected by oral AA, even at 5 mg/kg per d, and that excessive AA may aggravate inflammation, whereas AA shows no effects in rats without inflammatory bowel disease.

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Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease

Mediators of Inflammation ◽

10.1155/2020/6020247 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Zhongquan Xin ◽

Zhenya Zhai ◽

Hongrong Long ◽

Fan Zhang ◽

Xiaojun Ni ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Arachidonic Acid ◽

Bowel Disease ◽

Acid Metabolism ◽

Therapeutic Targets ◽

Liver Disorder ◽

Liver Disorders ◽

Cecropin A ◽

Inflammatory Bowel ◽

Orbitrap Ms

Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, p<0.05) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process.

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Fish oil-enriched diet is mucosal protective against acetic acid-induced colitis in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y91-072 ◽

1991 ◽

Vol 69 (4) ◽

pp. 480-487 ◽

Cited By ~ 42

Author(s):

Lonnie R. Empey ◽

Laurence D. Jewell ◽

Manohar L. Garg ◽

Alan B. R. Thomson ◽

M. Thomas Clandinin ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Acetic Acid ◽

Arachidonic Acid ◽

Fatty Acid ◽

Eicosapentaenoic Acid ◽

Fish Oil ◽

Polyunsaturated Fatty Acid ◽

Bowel Disease ◽

Fluid Absorption ◽

Inflammatory Bowel

Products of arachidonic acid metabolism are elevated in patients with inflammatory bowel disease and this elevation is correlated with disease activity. Eicosapentaenoic acid competes with arachidonic acid and alters eicosanoid biosynthesis. In this experiment, the possibility that eicosapentaenoic acid could be used in the treatment of inflammatory bowel disease was investigated by determining the effect of 6 weeks of a fish oil-supplemented diet, enriched in eicosapentaenoic acid, on colonic and ileal morphology, histology, and in vivo fluid absorption in rats with 4% acetic acid-induced colitis. The results of an eicosapentaenoic acid-enriched diet were compared with results of saturated and polyunsaturated fatty acid-enriched diets. In rats with misoprostol pretreated acetic acid-induced colitis, an eicosapentaenoic acid-enriched diet reversed net colonic fluid secretion to absorption and prevented macroscopic and histologic injury, compared with saturated and polyunsaturated fatty acid-enriched diets, which did not. The fish oil mucosal protective effect occurred in the presence of a 30-fold enhancement of PGE2 synthesis. In rats with non-misoprostol pretreated acetic acid-induced colitis, an eicosapentaenoic acid-enriched diet returned ileal fluid absorption to control levels, as compared with saturated and polyunsaturated fatty acid-enriched diets, which did not. In conclusion, a fish oil (eicosapentaenoic acid)-enriched diet, but not a saturated-or a polyunsaturated-enriched diet, protected colonic and ileal net fluid absorption in an experimental model of inflammatory bowel disease.Key words: eicosapentaenoic acid, fish oil, colitis, inflammatory bowel disease, leukotrienes, prostaglandins, misoprostol.

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Phospholipid turnover in the inflamed intestinal mucosa: Arachidonic acid-rich phosphatidyl/plasmenyl-ethanolamine in the mucosa in inflammatory bowel disease

Journal of Gastroenterology ◽

10.1007/s005350050215 ◽

1999 ◽

Vol 34 (1) ◽

pp. 46-53 ◽

Cited By ~ 24

Author(s):

Hiroyoshi Morita ◽

Kazuko Nakanishi ◽

Taeko Dohi ◽

Etsuko Yasugi ◽

Mieko Oshima

Keyword(s):

Inflammatory Bowel Disease ◽

Arachidonic Acid ◽

Intestinal Mucosa ◽

Bowel Disease ◽

Phospholipid Turnover ◽

Inflammatory Bowel

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Increased arachidonic acid levels in phospholipids of human colonic mucosa in inflammatory bowel disease

Clinical Science ◽

10.1042/cs0730361 ◽

1987 ◽

Vol 73 (4) ◽

pp. 361-364 ◽

Cited By ~ 49

Author(s):

Sergio Pacheco ◽

Keith Hillier ◽

Colin Smith

Keyword(s):

Ulcerative Colitis ◽

Inflammatory Bowel Disease ◽

Arachidonic Acid ◽

Oleic Acid ◽

Fatty Acid ◽

Stearic Acid ◽

Palmitic Acid ◽

Bowel Disease ◽

Colonic Mucosa ◽

Inflammatory Bowel

1. Colonic mucosa from 19 patients with ulcerative colitis, eight with Crohn's disease and 14 controls were analysed for arachidonic acid (C20:4), linoleic acid (C18:2), oleic acid (C18:1), stearic acid (C18:0) and palmitic acid (C16:0). 2. Gas–liquid chromatography of lipid extracts showed that arachidonic acid was significantly higher in ulcerative colitis (19 ± 4) and Crohn's disease (20 ± 3) than in controls (13 ± 5 μg/mg of protein) (means ± sd). Neither the degree of inflammation nor treatment with sulphasalazine or prednisolone appeared to influence the fatty acid concentrations. 3. Seventy-five to ninety-five per cent of the arachidonic acid was found in the phospholipid fraction after separation by thin-layer chromatography. There were no significant changes in the concentrations of the other fatty acids measured, although oleic acid was lower in inflammatory bowel disease. The ratios of oleic acid to stearic acid and to palmitic acid were lower in inflammatory bowel disease. 4. The alteration in the fatty acid profile may partly explain the increased synthesis of eicosanoids in colonic mucosa in inflammatory bowel disease.

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