Decreased Drug Penetration in Inflamed Tissue Related to Changed Mucosal Metabolism in Experimental Colitis

Pellequer, Yann; Weissenborn, Verena; Lamprecht, Alf

doi:10.1002/jps.20826

Cited by 8 publications

(2 citation statements)

References 21 publications

(28 reference statements)

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“…[29] However, CYP 3A expression is altered in the experimental colitis. [30] While the role of CYPs in IBD is not known, NR is involved in the mediation of inflammatory processes and therefore may play a role in the development of IBD. [3132] In fact, a significant down-regulation of PXR and the PXR target gene, MDR1, is observed in healthy mucosa adjacent to diseased colonic and terminal ileum of patients with CD and UC.…”

Section: Discussionmentioning

confidence: 99%

Protein expression analysis of inflammation-related colon carcinogenesis

Yasui

Tanaka

2009

J Carcinog

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Background:Chronic inflammation is a risk factor for colorectal cancer (CRC) development. The aim of this study was to determine the differences in protein expression between CRC and the surrounding nontumorous colonic tissues in the mice that received azoxymethane (AOM) and dextran sodium sulfate (DSS) using a proteomic analysis.Materials and Methods:Male ICR mice were given a single intraperitoneal injection of AOM (10 mg/kg body weight), followed by 2% (w/v) DSS in their drinking water for seven days, starting one week after the AOM injection. Colonic adenocarcinoma developed after 20 weeks and a proteomics analysis based on two-dimensional gel electrophoresis and ultraflex TOF/TOF mass spectrometry was conducted in the cancerous and nontumorous tissue specimens.Results:The proteomic analysis revealed 21 differentially expressed proteins in the cancerous tissues in comparison to the nontumorous tissues. There were five markedly increased proteins (beta-tropomyosin, tropomyosin 1 alpha isoform b, S100 calcium binding protein A9, and an unknown protein) and 16 markedly decreased proteins (Car1 proteins, selenium-binding protein 1, HMG-CoA synthase, thioredoxin 1, 1 Cys peroxiredoxin protein 2, Fcgbp protein, Cytochrome c oxidase, subunit Va, ETHE1 protein, and 7 unknown proteins).Conclusions:There were 21 differentially expressed proteins in the cancerous tissues of the mice that received AOM and DSS. Their functions include metabolism, the antioxidant system, oxidative stress, mucin production, and inflammation. These findings may provide new insights into the mechanisms of inflammation-related colon carcinogenesis and the establishment of novel therapies and preventative strategies to treat carcinogenesis in the inflamed colon.

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Section: Discussionmentioning

confidence: 99%

Protein expression analysis of inflammation-related colon carcinogenesis

Yasui

Tanaka

2009

J Carcinog

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“…Two studies render potential explanations for the different dose requirements among patients: tacrolimus is a substrate for the apically directed efflux transporter P-glycoprotein (P-gp) and also for cytochrome P450 3A (CYP3A). Elevated intestinal P-gp could result in decreased tacrolimus absorption, thereby leading to decreased blood concentration and clinical efficacy [ 51,52 ] .…”

Section: Special Precautions and Side Effects To Consider When Using mentioning

confidence: 99%

Conventional Medical Management of Ulcerative Colitis: Tacrolimus

Baumgart

2011

Crohn's Disease and Ulcerative Colitis

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Regulation of Drug Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer

Morgan

Lee

Nyagode

2012

Encyclopedia of Drug Metabolism and Interactions

146

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Under conditions of innate immune system activation (i.e., inflammation), the functions of specific cytochrome P450 enzymes, other drug metabolizing enzymes (DMEs), and drug transporters (DTs) are altered in the liver, small intestine, lung, kidney, and central nervous system (CNS). Many of these effects are primarily manifest at the transcriptional/RNA level, leading to corresponding changes in protein levels and function. This not only leads to altered drug and xenobiotic toxicity and action in diseased humans, but also has importance for disease therapy with biologic drugs that target inflammatory mediators or their receptors. Major roles for proinflammatory cytokines such as interleukin‐6 (IL‐6), IL‐1β, and tumor necrosis factor‐α(TNFα) are inferred from the abilities of these agents to affect DMEs and DTs in cultured cells and in vivo , but the in vivo contributions of cytokines to regulation of these proteins in different inflammatory disease states is still poorly understood.

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Decreased Drug Penetration in Inflamed Tissue Related to Changed Mucosal Metabolism in Experimental Colitis

Cited by 8 publications

References 21 publications

Protein expression analysis of inflammation-related colon carcinogenesis

Protein expression analysis of inflammation-related colon carcinogenesis

Conventional Medical Management of Ulcerative Colitis: Tacrolimus

Regulation of Drug Metabolizing Enzymes and Transporters in Infection, Inflammation, and Cancer

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