51. Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection.
- Author
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Hamza AR, Krasniqi AS, Srinivasan PK, Afify M, Bleilevens C, Klinge U, and Tolba RH
- Subjects
- Alanine Transaminase blood, Animals, Cell Proliferation drug effects, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Enterocytes drug effects, Enterocytes metabolism, Enterocytes pathology, Gastrointestinal Transit drug effects, Gene Expression Regulation, 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 metabolism, Intestine, Small pathology, Intestine, Small physiopathology, Lipid Peroxidation drug effects, Liver blood supply, Liver metabolism, Liver pathology, Liver physiopathology, Liver Circulation drug effects, Liver Cirrhosis diagnosis, Liver Cirrhosis genetics, Liver Cirrhosis metabolism, Liver Cirrhosis physiopathology, Liver Regeneration drug effects, Male, Malondialdehyde blood, Meloxicam, Microcirculation drug effects, RNA, Messenger metabolism, Rats, Wistar, Time Factors, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 metabolism, Cyclooxygenase 2 Inhibitors pharmacology, Hepatectomy, Intestine, Small drug effects, Liver drug effects, Liver surgery, Liver Cirrhosis therapy, Thiazines pharmacology, Thiazoles pharmacology
- Abstract
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 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., Conclusion: 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.
- Published
- 2014
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