title: Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection.
abstract: OBJECTIVE
  To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Astrit R
authors.initials: AR
authors.lastname: Hamza
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Avdyl S
authors.initials: AS
authors.lastname: Krasniqi
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Pramod Kadaba
authors.initials: PK
authors.lastname: Srinivasan
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Mamdouh
authors.initials: M
authors.lastname: Afify
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bleilevens
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Klinge
authors.affiliation: Astrit R Hamza, Pramod Kadaba Srinivasan, Mamdouh Afify, René H Tolba, Institute for Laboratory Animal Science and Experimental Surgery, University Hospital Rheinisch-Westfälische Technische Hochschule Aachen, 52074 Aachen, Germany.
authors.forename: René H
authors.initials: RH
authors.lastname: Tolba
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005772:Gastrointestinal Transit / Q000187:drug effects; D005786:Gene Expression Regulation; D006498:Hepatectomy; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007421:Intestine, Small / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008115:Liver Regeneration / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D000077239:Meloxicam; D008833:Microcirculation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D013843:Thiazines / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D012333:RNA, Messenger; C508962:Tgfb1 protein, rat; D013843:Thiazines; D013844:Thiazoles; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D000410:Alanine Transaminase; D000077239:Meloxicam
keywords: Cyclooxigenase-2; Gut-liver axis; Liver cirrhosis; Liver resection; Meloxicam; Microcirculation