Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion

BACKGROUND The Pringle maneuver[portal triad obstruction(PTO)]provides huge disturbances during ischemia and even more thereafter in reperfusion.Contrarily,a possible solution may be stable gastric pentadecapeptide BPC 157,with already documented beneficial effects in ischemia/reperfusion conditions.Recently,BPC 157,as a cytoprotective agent,successfully resolved vessel occlusions in rats(ischemic colitis;deep vein thrombosis,superior anterior pancreaticoduodenal vein;bile duct cirrhosis)through rapid collateral vessel recruitment to circumvent vessel occlusion.Thereby,medication BPC 157 regimens were administered as a single challenge before and during ischemia or,alternatively,at various time points during reperfusion.AIM To introduce BPC 157 therapy against pringle maneuver-damage.METHODS In deeply anesthetised rats,the portal triad was clamped up for 30 min.Rats then underwent reperfusion for either 15 min or 24 h.Medication[(10μg,10 ng/kg)regimens,administered as a single challenge]picked(a)ischemia,PTO period[at 5 min before(ip)or at 5 or 30 min of ligation time(as a bath to PTO)]or(b)reperfusion,post-PTO period[at 1 or 15 min(bath during surgery)or 24 h(ip)reperfusion-time].We provided gross,microscopy,malondialdehyde,serum enzymes,electrocardiogram,portal,caval,and aortal pressure,thrombosis and venography assessments.RESULTS BPC 157 counteracts electrocardiogram disturbances(increased P wave amplitude,S1Q3T3 QRS pattern and tachycardia).Rapidly presented vascular pathway(portal vein-superior mesenteric vein-inferior mesenteric vein-rectal veins-left ileal vein-inferior caval vein)as the adequate shunting immediately affected disturbed haemodynamics.Portal hypertension and severe aortal hypotension during PTO,as well as portal and caval hypertension and mild aortal hypotension in reperfusion and refractory ascites formation were markedly attenuated(during PTO)or completely abrogated(reperfusion);thrombosis in portal vein tributaries and inferior caval vein or hepatic artery was counteracted during portal triad obstruction PTO.Also,counteraction included the whole vicious injurious circle[i.e.,lung pathology(severe capillary congestion),liver(dilated central veins and terminal portal venules),intestine(substantial capillary congestion,submucosal oedema,loss of villous architecture),splenomegaly,right heart(picked P wave values)]regularly perpetuated in ischemia and progressed by reperfusion in Pringle rats.CONCLUSION BPC 157 resolves pringle maneuver-damage in rats,both for ischemia and reperfusion.

Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in ratsPentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

BACKGROUND Recently,as a possible therapy resolving solution,pentadecapeptide BPC 157 therapy,has been used in alleviating various vascular occlusion disturbances.BPC 157 was previously reviewed as novel mediator of Robert cytoprotection and endothelium protection in the stomach,and gut-brain axis,beneficial therapy in gastrointestinal tract,with particular reference to vascular recruitment,ulcerative colitis and tumor cachexia,and other tissues healing.Here we raised new hypothesis about BPC 157 therapy in the Budd-Chiari syndrome in rats,rapid bypassing of the suprahepatic inferior caval vein occlusion,and rats recovery with the active and effective pharmacotherapy treatment.AIM To investigate Budd-Chiari syndrome model(inferior caval vein suprahepatic occlusion)resolution,since BPC 157 resolves various rat vascular occlusion.METHODS We assessed the activated bypassing pathways between the inferior and superior caval veins and portocaval shunt,counteracted caval/portal hypertension,aortal hypotension,venous/arterial thrombosis,electrocardiogram disturbances,liver and gastrointestinal lesions(i.e.,stomach and duodenum hemorrhages,in particular,congestion).Rats with suprahepatic occlusion of the inferior vena cava by ligation were medicated at 1 min,15 min,24 h,or 48 h post-ligation.Medication consisted of 10μg/kg BPC 157,10 ng BPC 157 or 5 m L/kg saline,administered once as an abdominal bath or intragastric application.Gross and microscopic observations were made,in addition to assessments of electrical activity of the heart(electrocardiogram),portal and caval hypertension,aortal hypotension,thrombosis,hepatomegaly,splenomegaly and venography.Furthermore,levels of nitric oxide,malondialdehyde in the liver and serum enzymes were determined.RESULTS BPC 157 counteracted increased P wave amplitude,tachycardia and ST-elevation,i.e.,right heart failure from acute thrombotic coronary occlusion.The bypassing pathway of the inferior vena cava-azygos(hemiazygos)vein-superior vena cava and portocaval shunt occurred rapidly.Even with severe caval portal hypertension,BPC 157 antagonized portal and caval hypertension and aortal hypotension,and also reduced refractory ascites.Thrombosis of portal vein tributaries,inferior vena cava,and hepatic and coronary arteries was attenuated.In addition,there was reduced pathology of the lungs(severe capillary congestion)and liver(dilated central veins and terminal portal venules),decreased intestine hemorrhagic lesions(substantial capillary congestion,submucosal edema and architecture loss),and increased liver and spleen weight.During the period of ligation,nitric oxide-and malondialdehyde-levels in the liver remained within normal healthy values,and increases in serum enzymes were markedly reduced.CONCLUSION BPC 157 counteracts Budd Chiari syndrome in rats.

Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157,L-NAME and L-arginine in rats

BACKGROUND After parietal peritoneum excision with an underlying superficial layer of muscle tissue in rats,there is failed vasculature,and finally,increased adhesion formation.We hypothesized that unlike nitric oxide(NO)-agents,L-NAME and/or L-arginine,the application of the stable gastric pentadecapeptide BPC 157 with its most recent vascular effects(“vascular recruitment”)means attenuated bowel adhesion formation and NO-and malondialdehyde(MDA)-tissue values.AIM To focused on the bowel adhesion and the therapy with the BPC 157,its most and application of NO-agents.METHODS Along with defect creation,medication was(1)during surgery,once,at 1 min after defect creation as an abdominal bath(1 mL/rat),BPC 157(10μg/kg,10 ng/kg,1 mL/rat),an equivolume of saline,L-NAME(5 mg/kg),L-arginine(200 mg/kg)alone and/or combined.Alternatively,medication was(2)intraperitoneally once daily,first application at 30 min after surgery,last application 24 h before assessment at d 7 or d 14.As a postponed therapy to preexisting adhesion(3),BPC 157(10μg/kg,10 ng/kg intraperitoneally,1 mL/rat)was given once daily since d 7.RESULTSThe recovery effect of the BPC 157 regimens goes with the presence of abundant vascular vessels in and near the defect,which occurs rapidly.Lastly,also applied as post-treatment,BPC 157 creates attenuated adhesions,minimal or no adhesion.Contrarily,NO-agents have diverse initial and final effects:The initial weakening of blood vessel disappearance and finally,severe worsening of adhesions(LNAME)vs the initial weakening of blood vessel disappearance and finally,attenuation of adhesions formation(L-arginine),which counteract each other response given together.Importantly,BPC 157 maintains its beneficial effect also when given with NO-agents(L-NAME+BC 157;L-arginine+BPC 157;L-NAME+L-arginine+BPC 157).Finally,with respect to the increased NO-and MDAvalues-adhesion tissue formation relation,unlike diverse effect of the NO-agents,the BPC 157 application effect regularly combines decrease on the increased NOand MDA-values and the beneficial outcome(less adhesion formation).CONCLUSION BPC 157 therapy can be suited for the realization of the peritoneal defect healing with minimal or no adhesion formation.