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Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection.

World journal of gastroenterology (2014-10-31)
Astrit R Hamza, Avdyl S Krasniqi, Pramod Kadaba Srinivasan, Mamdouh Afify, Christian Bleilevens, Uwe Klinge, René H Tolba
ZUSAMMENFASSUNG

To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection. Forty-four male Wistar rats were assigned to three groups: (1) control group (CG); (2) bile duct ligation with meloxicam treatment (BDL + M); and (3) bile duct ligation without meloxicam treatment (BDL). Secondary biliary liver cirrhosis was induced via ligature of the bile duct in the BDL + M and BDL groups. After 2 wk, the animals underwent a 50% hepatectomy. In the BDL + M group 15 min prior to the hepatectomy, one single dose of meloxicam was administered. Parameters measured included: microcirculation of the liver and small bowel; portal venous flow (PVF); gastrointestinal (GI) transit; alanine aminotransferase (ALT); malondialdehyde; interleukin 6 (IL-6), transforming growth factor beta 1 (TGF-β1) and hypoxia-inducible factor 1 alpha (HIF-1α) levels; mRNA expression of cyclooxigenase-2 (COX-2), IL-6 and TGF-β1; liver and small bowel histology; immunohistochemical evaluation of hepatocyte and enterocyte proliferation with Ki-67 and COX-2 liver expression. Proliferative activity of hepatocytes after liver resection, liver flow and PVF were significantly higher in CG vs BDL + M and CG vs BDL group (P < 0.05), whereas one single dose of meloxicam ameliorated liver flow and proliferative activity of hepatocytes in BDL + M vs BDL group. COX-2 liver expression at 24 h observation time (OT), IL-6 concentration and mRNA IL-6 expression in the liver especially at 3 h OT, were significantly higher in BDL group when compared with the BDL + M and CG groups (P < 0.01, P < 0.001, P < 0.01, respectively). Liver and small bowel histology, according to a semi quantitative scoring system, showed better integrity in BDL + M and CG as compared to BDL group. ALT release and HIF-1α levels at 1 h OT were significantly higher in BDL + M compared to CG and BDL group (P < 0.001 and P < 0.01, respectively). Moreover, ALT release levels at 3 and 24 h OT were significantly higher in BDL group compared to CG, P < 0.01. GI transit, enterocyte proliferative activity and number of goblet cells were in favor of meloxicam treatment vs BDL group (P < 0.05, P < 0.001, P < 0.01, respectively). Additionally, villus length were higher in BDL + M as compared to BDL group. One single dose of meloxicam administered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Benzol, suitable for HPLC, ≥99.9%
Sigma-Aldrich
Benzol, ACS reagent, ≥99.0%
Sigma-Aldrich
Benzol, puriss. p.a., reag. Ph. Eur., ≥99.7%
Supelco
Benzol, analytical standard
Sigma-Aldrich
Benzol, anhydrous, 99.8%
Supelco
Cefuroxim Natriumsalz
Sigma-Aldrich
4,5-Dihydroxy-anthrachinon-2-carbonsäure, technical grade
Sigma-Aldrich
4,5-Dihydroxy-anthrachinon-2-carbonsäure
Supelco
Benzol, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Cefuroximnatrium, United States Pharmacopeia (USP) Reference Standard
Cefuroxim-Natrium, European Pharmacopoeia (EP) Reference Standard