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

• Published in: World journal of gastroenterology : WJG 2014-10, Vol.20 (40), p.14841-14854
• Main Authors: Hamza, Astrit R, Krasniqi, Avdyl S, Srinivasan, Pramod Kadaba, Afify, Mamdouh, Bleilevens, Christian, Klinge, Uwe, Tolba, René H
• Format: Article
• Language: English
• Subjects: Alanine Transaminase - blood; Animals; axis; Cell Proliferation - drug effects; cirrhosis; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Enterocytes - drug effects; Enterocytes - metabolism; Enterocytes - pathology; Gastrointestinal Transit - drug effects; Gene Expression Regulation; Gut-liver; Hepatectomy; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Intestine, Small - blood supply; Intestine, Small - drug effects; Intestine, Small - metabolism; Intestine, Small - pathology; Intestine, Small - physiopathology; Lipid Peroxidation - drug effects; Liver; Liver - blood supply; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - physiopathology; Liver - surgery; Liver Circulation - drug effects; Liver Cirrhosis - diagnosis; Liver Cirrhosis - genetics; Liver Cirrhosis - metabolism; Liver Cirrhosis - physiopathology; Liver Cirrhosis - therapy; Liver Regeneration - drug effects; Male; Malondialdehyde - blood; Mel; Microcirculation - drug effects; Original; Rats, Wistar; resection; RNA, Messenger - metabolism; Thiazines - pharmacology; Thiazoles - pharmacology; Time Factors; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v20.i40.14841

AIM: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 ligatureof the bile duct in the BDL+M and BDL groups.After 2wk,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 24h 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-1αlevels 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.CONCLUSION:One single dose of meloxicam admin-istered after cirrhotic liver resection was able to cause better function and integrity of the remaining liver and small bowel.