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

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.

Novel synthetic adhesive as an effective alternative to Fibrin based adhesives

AIM To compare a novel, fully synthetic, polyurethane based glue(MAR-1) to fibrin sealant in a partial liver resection rat model.METHODS After 50% resection of the lateral left liver lobe in male Wistar rats(n = 7/group/time point), MAR-1, Fibrin or Na Cl was applied. After 14, 21 and 90 postoperative days, sealant degradation, intra-abdominal adhesions were scored, and histological examination of liver tissue was performed.RESULTS(Mean ± SEM)(MAR-1 vs Fibrin vs Na Cl). Bleeding mass was significantly higher in Na Cl(3.36 ± 0.51 g)compared to MAR-1(1.44 ± 0.40 g) and Fibrin(1.16 ± 0.32 g). At 14 and 90 d, bleeding time was significantly lower in MAR-1(6.00 ± 0.9 s; 13.57 ± 3.22 s) and Fibrin(3.00 ± 0.44 s; 22.2 ± 9.75 s) compared to Na Cl(158.16 ± 11.36 s; 127.5 ± 23.3 s). ALT levels were significantly higher in MAR-1(27.66 ± 1 U/L) compared to Fibrin(24.16 ± 0.98 U/L) and Na Cl(23.85 ± 0.80 U/L). Intrabdominal adhesions were significantly lower in MAR-1(11.22% ± 5.5%) compared to Na Cl(58.57% ± 11.83%). Degradation of the glue was observed and MAR-1 showed almost no traces of glue in the abdominal cavity as compared to the Fibrin(10% ± 5% 14 d; 7% ± 3% 21 d). Survival showed no significant differences between the groups.CONCLUSION Compared to Fibrin, MAR-1 showed similar hemostatic properties, no adverse effects, and is biocompatible. Further studies on adhesion strength and biodegradability of synthetic sealants are warranted.