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The impact of infla...
The impact of inflammation on the expression of drug transporters and metabolic enzymes in colonic tissue from ulcerative colitis patients
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- de Waal, Tom (författare)
- Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.
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- Handin, Niklas (författare)
- Uppsala universitet,Institutionen för farmaci
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- Brouwers, Joachim (författare)
- Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.
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- Ferrante, Marc (författare)
- Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium.;Katholieke Univ Leuven, Translat Res Ctr Gastrointestinal Disorders, TARGID, Leuven, Belgium.
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- Vermeire, Severine (författare)
- Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium.;Katholieke Univ Leuven, Translat Res Ctr Gastrointestinal Disorders, TARGID, Leuven, Belgium.
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- Vanuytsel, Tim (författare)
- Univ Hosp Leuven, Dept Gastroenterol & Hepatol, Leuven, Belgium.;Katholieke Univ Leuven, Translat Res Ctr Gastrointestinal Disorders, TARGID, Leuven, Belgium.
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- Artursson, Per (författare)
- Uppsala universitet,Institutionen för farmaci
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- Augustijns, Patrick (författare)
- Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium.
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Katholieke Univ Leuven, Drug Delivery & Disposit, Leuven, Belgium Institutionen för farmaci (creator_code:org_t)
- Elsevier, 2022
- 2022
- Engelska.
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Ingår i: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 628
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The intestinal tract forms an important barrier against xenobiotics while allowing nutrients to pass. In ulcerative colitis (UC), a chronic inflammatory bowel disease, this barrier function is impaired leading to an abnormal immune response and inflammation of the colonic mucosa. Transporter proteins and metabolic enzymes are an integral part of the protective barrier in the gut and play an important role in the disposition of nutrients, toxins and oral drugs. In this study, the protein expression of 13 transporters and 13 enzymes was determined in the sigmoid and rectum of UC patients in endoscopic remission and during active inflammation. In inflamed con-ditions (endoscopic Mayo sub-score 1, 2 or 3), a significant decrease (q < 0.05) was observed in the median expression of the transporters P-gp (0.046 vs 0.529 fmol/mu g protein), MRP4 (0.003 vs 0.023 fmol/mu g protein) and MCT1 (0.287 vs 1.090 fmol/mu g protein), and the enzymes CYP3A5 (0.031 vs 0.046 fmol/mu g protein) and UGT2B7 (0.083 vs 0.176 fmol/mu g protein). Moreover, during severe inflammation, the decrease was even more pro-nounced. Expression levels of other proteins were not altered during inflammation (e.g., OATP2B1, CYP3A4, CYP2B6 and UGT2B15). The results suggest a decreased transport and metabolism of xenobiotics in the colon of UC patients during active inflammation potentially altering local drug concentrations and thus treatment outcome.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- Drug Absorption
- Drug transporters
- Metabolic enzymes
- Colon
- Proteomics
- Ulcerative Colitis
- Inflammation
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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