Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil‐specific antibacterial clearance

Bettenworth, Dominik; Nowacki, Tobias M.; Ross, Matthias; Kyme, Pierre; Schwammbach, Daniela; Kerstiens, Linda; Thoennissen, Gabriela B.; Bokemeyer, Carsten; Hengst, K; Berdel, Wolfgang E.; Heidemann, Jan; Thoennissen, Nils H.

doi:10.1002/mnfr.201300818

Cited by 32 publications

(32 citation statements)

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“…IBD is bound to be closely related to the metabolic disorder of bile acids, especially to reduce the level of secondary bile acids, while hydrophilic secondary bile acids have cytoprotective effects. In this study, the down-regulation of taurodeoxycholic acid, chenodeoxycholic acid and bile acid in plasma of colitis rats was verified this point ( Blackwood et al, 2011 ; Disher et al, 2014 ).…”

Section: Discussionsupporting

confidence: 68%

“…Compared with the normal group, the levels of niacinamide in TNBS-induced colitis was decreased. Studies have shown that nicotinamide enhanced the antimicrobial activity of neutrophil, improved tissue damage and reduced the activity of MPO of DSS-induced colitis mice significantly ( Disher et al, 2014 ; Dominik et al, 2014 ). Consistent with previous studies, the levels of linoleic acid and arachidonic acid were decreased and the leukotriene A4 was increased in colitis rats.…”

Section: Discussionmentioning

confidence: 99%

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Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways

et al. 2018

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Studies have indicated that Chrysanthemum polysaccharides (CP) could prominently ameliorate colitis rats, but its possible mechanism remains unclear. In this study, the underlying mechanism of CP was explored by the metabolic profiling analysis and correlated signaling pathways. TNBS/ethanol induced colitis was used to investigate the intervention efficacy following oral administration of CP. The levels of cytokines such as TNF-α, IL-6, IFN-γ and IL-1β, and the activities of SOD, MPO, and MDA were determined. We also performed western-blot for p65, TLR4, p-JAK2, and STAT3 protein expression in the colon tissue to probe their mechanisms of correlated signaling pathways. What’s more, the metabolic changes in plasma and urine from colitis rats were investigated based on UPLC-Q-TOF/MS combined with MetabolynxTM software. The potential biomarkers and metabolic pathways were also tentatively confirmed. The metabolic profiles of plasma and urine were clearly improved in model rats after oral administration of CP. Thirty-two (17 in serum and 15 in urine) potential biomarkers were identified. The endogenous metabolites were mainly involved in linoleic acid, retinol, arachidonic acid, glycerophospholipid and primary bile acid metabolism in plasma, and nicotinate and nicotinamide, ascorbate and aldarate, histidine and β-alanine metabolism in urine. After polysaccharides intervention, these markers turned back to normal level at some extent. Meanwhile, the elevated expression levels of pp65, TLR4, p-STAT3, and p-JAK2 were significantly decreased after treatment. Results suggested that CP would be a potential prebiotics for alleviation of TNBS-induced colitis. The study paved the way for the further exploration of the pathogenesis, early diagnosis and curative drug development of the colitis.

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Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways

et al. 2018

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“…In human gastroenterology, the evaluation of serum AAs is a non-invasive, predictive marker of intestinal inflammation, and the supplementation of AAs can attenuate this inflammation and improve clinical signs and weight gain [7,8].…”

Section: Introductionmentioning

confidence: 99%

Serum amino acid profile in 51 dogs with immunosuppressant-responsive enteropathy (IRE): a pilot study on clinical aspects and outcomes

et al. 2020

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Background: Lower levels of tryptophan (TRP) have been identified in people with inflammatory bowel disease and in dogs with protein-losing enteropathy (PLE). No data on serum amino acids (AAs) but some on plasma in canine immunosuppressant-responsive enteropathy (IRE) are available. The aim of this study is to compare serum AAs between healthy and IRE dogs, considering clinicopathological variables and follow-up. Results: Twenty-six healthy control dogs (CD) and 51 IRE dogs were included. IRE was diagnosed after the exclusion of extra-intestinal diseases and food and antibiotic responsive enteropathies. The canine chronic enteropathy clinical activity index (CCECAI) was assessed at presentation and during the clinical follow-up. In CD and IRE dogs, 19 different serum AAs were measured. IRE dogs were classified into responders, partial responders and non-responders, based on CCECAI after 1 month, and divided into PLE and non-PLE, based on albumin level. IRE dogs showed lower L-Tyrosine (TYR), L-Phenylalanine (PHE) and TRP (p < 0.001) and higher L-Serine (SER), L-Glutamic acid (GLU), L-Arginine (p < 0.001), L-Threonine (p = 0.013), Proline (p = 0.044), L-Cysteine (p = 0.003), L-Valine (p = 0.018), L-Lysine (p = 0.01) and L-Isoleucine (p = 0.005) than CDs. PLE dogs showed lower L-Histidine (HIS) (p = 0.008), PHE (p = 0.005) and TRP (p = 0.005) than non-PLE dogs. In IRE dogs, median GLU was significantly lower in dogs with BCS 3/9 than BCS 5/9 category (p = 0.036). Total protein was positively correlated with PHE and TRP (both p = 0.031, r = 0.30) and albumin was positively correlated with HIS (p = 0.025, r = 0.31), PHE and TRP (both p = 0.001, r = 0.46). HIS (p = 0.041), PHE (p = 0.047) and TRP (p = 0.044) concentrations were significantly lower in nonresponders than in responders and partial responders. Conclusions:This study may suggest further investigation on serum, HIS, PHE, TRP and TYR as markers of intestinal disease and proposed HIS, PHE and TRP as prognostic marker for response to therapy.

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“…5,9,10 There is an anti-inflammatory effect of dietary intervention with tryptophan or tryptophan metabolites in experimental models of colitis, with supplementation ameliorating clinical signs, improving weight gain and histological scores and decreasing gut permeability and expression of proinflammatory cytokines. 11,12 Similarly, supplementation with glutamine, arginine, N-acetylcysteine, and glycine in animal models of IBD has beneficial effects such as reduced intestinal permeability and decreased production of proinflammatory cytokines. [13][14][15][16] Dogs with protein-losing enteropathy (PLE) have increased loss of protein from the intestinal tract resulting in hypoproteinemia.…”

mentioning

confidence: 99%

Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

Kathrani

Allenspach

Fascetti

et al. 2018

Veterinary Internal Medicne

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BackgroundCertain amino acids are decreased in humans with inflammatory bowel disease (IBD) and supplementation with the same amino acids has shown beneficial effects in animal models of IBD. Currently, the amino acid status of dogs with protein‐losing enteropathy (PLE) is unknown.Hypothesis/ObjectiveTo determine if serum amino acid concentrations are abnormal in dogs with PLE and correlated with clinical and laboratory variables and outcome.AnimalsThirty client‐owned dogs diagnosed with PLE and 12 apparently healthy dogs seen at Bristol Veterinary School.MethodsRetrospective study using stored residual serum from fasted dogs with PLE, collected at the time of diagnostic investigation and from apparently healthy dogs. Serum was analyzed for 30 amino acids using an automated high‐performance liquid chromatography amino acid analyzer.ResultsSerum tryptophan concentrations were significantly decreased in dogs with PLE (median, 22 nmol/mL; range, 1–80 nmol/mL) compared with apparently healthy control dogs (median, 77.5 nmol/mL; range, 42–135 nmol/mL, P < .001). There were no significant differences in the remaining 29 serum amino acids between dogs with PLE and apparently healthy. Serum tryptophan concentrations were also significantly correlated with serum albumin concentrations in dogs with PLE (P = .001, R 2 = 0.506).Conclusions and Clinical ImportanceDecreased serum tryptophan concentration might play a role in the pathogenesis of canine PLE or be a consequence of the disease.

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Nicotinamide treatment ameliorates the course of experimental colitis mediated by enhanced neutrophil‐specific antibacterial clearance

Abstract: Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).

Cited by 32 publications

References 52 publications

Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways

Polysaccharides From Chrysanthemum morifolium Ramat Ameliorate Colitis Rats via Regulation of the Metabolic Profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 Signaling Pathways

Serum amino acid profile in 51 dogs with immunosuppressant-responsive enteropathy (IRE): a pilot study on clinical aspects and outcomes

Alterations in serum amino acid concentrations in dogs with protein‐losing enteropathy

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