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| 1 | Esophagogastric anastomosis in rats: Improved healing by BPC 157 and L-arginine, aggravated by L-NAME显示文摘AIM To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. METHODS Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NOsystem. In the 4 d after esophagogastric anastomosis creation, rats received medication(/kg intraperitoneallyonce daily: BPC 157(10 μg, 10 ng), L-NAME(5 mg), or L-arginine(100 mg) alone and/or combined or BPC 157(10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage(sum of the longest diameters, mm), esophagitis(scored 0-5), weak anastomosis(m L H2 O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter(cm H2O), progressive weight loss(g) and mortality. Immediate effect assessed blood vessels disappearance(scored 0-5) at the stomach surface immediately after anastomosis creation. RESULTS BPC 157(all regimens) fully counteracted the perilous disease course from the very beginning(i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening(with L-NAME administration) and amelioration(with L-arginine), either L-arginine amelioration prevails(attenuated esophageal and gastric lesions) or they counteract each other(L-NAME + L-arginine); with the addition of BPC 157(L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability(as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening(obtained with L-NAME administration that was counteracted); or amelioration(L-arginine + BPC 157-rats correspond to BPC 157-rats).CONCLUSION Innate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy. | Zeljko Djakovic Ivka Djakovic Vedran Cesarec Goran Madzarac Tomislav Becejac Goran Zukanovic Domagoj Drmic Lovorka Batelja Anita Zenko Sever Danijela Kolenc Alen Pajtak Nikica Knez Mladen Japjec Kresimir Luetic Dinko Stancic-Rokotov Sven Seiwerth Predrag Sikiric | 2016 | World Journal of Gastroenterology2016，22，41： | 3 |
| 2 | 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显示文摘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. | Slaven Gojkovic Ivan Krezic Borna Vrdoljak Dominik Malekinusic Ivan Barisic andreja Petrovic Katarina Horvat Pavlov Marijan Kolovrat Antonija Duzel Mario Knezevic Katarina Kasnik Kovac Domagoj Drmic Lovorka Batelja Vuletic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric | 2020 | World Journal of Gastrointestinal Pathophysiology2020，11，1： | 2 |
| 3 | Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights显示文摘AIM To provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157. METHODS Medication [BPC 157,L-NAME,L-arginine(alone/combined),saline] was bath at the blood deprived colon segment. During reperfusion,medication was BPC 157 or saline. We recorded(USB microscope camera) vessel presentation through next 15 min of ischemic colitis(ICrats) or reperfusion(removed ligations)(IC + RL-rats);oxidative stress as MDA(increased(IC-and IC + RLrats)) and NO levels(decreased(IC-rats);increased(IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction(OB)] for 3 d(IC + OBrats),then received BPC 157 bath. RESULTS Commonly,in colon segment(25 mm,2 ligations on left colic artery and vein,3 arcade vessels within ligated segment),in IC-,IC + RL-,IC + OB-rats,BPC 157(10 μg/kg) bath(1 m L/rat) increased vessel presentation,inside/outside arcade interconnections quickly reappeared,mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME(5 mg) and L-arginine(100 mg). MDA-and NO-levels were normal in BPC 157 treated IC-rats and IC + RLrats. In addition,on day 10,BPC 157-treated IC + OBrats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects;the treated colon segment was of normal diameter,and only small adhesions were present.CONCLUSION BPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system. | Antonija Duzel Josipa Vlainic Marko Antunovic Dominik Malekinusic Borna Vrdoljak Mariam Samara Slaven Gojkovic Ivan Krezic Tinka Vidovic Zdenko Bilic Mario Knezevic Marko Sever Nermin Lojo Antonio Kokot Marijan Kolovrat Domagoj Drmic Jaksa Vukojevic Tamara Kralj Katarina Kasnik Marko Siroglavic Sven Seiwerth Predrag Sikiric | 2017 | World Journal of Gastroenterology2017，23，48： | 2 |
| 4 | Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME显示文摘AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib(1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157(known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine(100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester(L-NAME)](5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization(L-arginine) and NO system antagonization(L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157(at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups(L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition(counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade(equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement. | Domagoj Drmic Danijela Kolenc Spomenko Ilic Lara Bauk Marko Sever Anita Zenko Sever Kresimir Luetic Jelena Suran Sven Seiwerth Predrag Sikiric | 2017 | World Journal of Gastroenterology2017，23，29： | 2 |
| 5 | 十五肽BPC157减弱慢性苯丙胺诱导的行为障碍(英文)显示文摘AIM: To investigate the effect of pentadecapeptide BPC 157 on chronic exposure to amphetamine in rats, particularly the changes commonly referred in chronic amphetamine studies as tolerance ( lesser grade of stereotyped behavior, without increased excitability) and reverse tolerance (ie, prominent stereotyped behavior and heightened startle response upon late amphetamine challenges). METHODS: After initial application (initial single dose-regimen), amphetamine (10 mg/kg, ip) was given once daily till d 5 ( continuous administration-regimen), and thereafter on d 8, 16, and 46 (intermittent administration regimen). For stereotyped behavior and heightened startle response the observation period was 120 min after amphetamine application, and each animal was observed for 10 s in 5 min intervals. Pentadecapeptide BPC 157 (10 μg/kg or 10 ng/kg, ip) or saline (5.0 mL/kg, ip) were given only at the beginning of the experiment, simultaneously with the initial dose of amphetamine. RESULTS: In relation to | Predrag SIKIRIC, Nikola JELOVAC, Andjelka JELOVAC-GJELDUM, Goran DODIG, Mario STARESINIC, Tornislav ANIC, Ivan ZORICIC, Davor RAK, Darko PEROVIC, Gorana ARALICA, Gojko BULJAT, Ingrid PRKACEV, Martina LOVRIC-BENCIC, Jadranka SEPAROVIC, Sven SEIWERTH, Rudolf RUCMAN, Marijan PETEK, Branko TURKOVIC, Tihomil ZIGER, AJenka BOBAN-BLAGAIC, Vlado BEDEKOVIC, Ante TONKIC, Slaven BABIC ( Department of Pharmacology, Medical Faculty University of Zagreb, Croatia) | 2002 | Acta Pharmacologica Sinica2002，23，5： | 2 |
| 6 | Pentadecapeptide BPC 157 resolves Pringle maneuver in rats,both ischemia and reperfusion显示文摘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. | Marijan Kolovrat Slaven Gojkovic Ivan Krezic Dominik Malekinusic Borna Vrdoljak Katarina Kasnik Kovac Tamara Kralj Domagoj Drmic Ivan Barisic Katarina Horvat Pavlov Andreja Petrovic Antonija Duzel Mario Knezevic Ivan Mirkovic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric | 2020 | World Journal of Hepatology2020，12，5： | 1 |
| 7 | BPC-157,一种胃十五肽的抗焦虑作用:休克探查/埋藏试验和明暗试验(英文)显示文摘AIM: To study anxiolytic effect of a gastric pentade-capeptide, BPC-157. METHODS: In shock probe/burying test, pentadecapeptide BPC-157 (10 μg/kg, 10ng/kg, ip), diazepam (0.075, 0.0375 mg/kg, ip),and an equivolume of saline (5 mL/kg, ip) were givenat 30 min prior test. In light/dark test, the same dosageof diazepam, BPC-157, and saline were given at 45 minPrior procedure. RESULTS: Shock probe/buryingtest: rats treated with either diazepam or pentadecapeptideBPC-157 were much less afraid after the shock: | Predrag SIKIRIC Nikola JELOVAC Andjelka JELOVAC-GJELDUM Goran DODIG Mario STARESINIC Tomislav ANIC Ivan ZORICIC Darko PEROVIC Gorana ARALICA Gojko BULJAT Ingrid PRKACIN Martina LOVRIC-BENCIC Jadranka SEPAROVIC Sven SEIWERTH Rudolf RUCMAN Marijan PETEK Branko TURKOVIC Tihomil ZIGER | 2001 | Acta Pharmacologica Sinica2001，22，3： | 1 |
| 8 | Counteraction of perforated cecum lesions in rats: Effects of pentadecapeptide BPC 157,L-NAME and L-arginine显示文摘AIM To study the counteraction of perforated cecum lesion using BPC 157 and nitric oxide(NO) system agents.METHODS Alongside with the agents' application(after 1 min, medication(/kg, 10 ml/2 min bath/rat) includes: BPC 157(10 μg), L-NAME(5 mg), L-arginine(100mg) alone or combined, and saline baths(controls)) on the rat perforate cecum injury, we continuously assessed the gross reappearance of the vessels(USB microcamera) quickly propagating toward the defect at the cecum surface, defect contraction, bleeding attenuation, MDA-and NO-levels in cecum tissue at 15 min, and severity of cecum lesions and adhesions at 1 and 7 d. RESULTS Post-injury, during/after a saline bath, the number of vessels was significantly reduced, the defect was slightly narrowed, bleeding was significant and MDA-levels increased and NO-levels decreased. BPC 157 bath: the vessel presentation was markedly increased, the defect was noticeably narrowed, the bleeding time was shortened and MDA-and NO-levels remained normal. L-NAME: reduced vessel presentation but not more than the control, did not change defect and shortened bleeding. L-arginine: exhibited less vessel reduction, did not change the defect and prolonged bleeding. In combination, mutual counteraction occurred(L-NAME + L-arginine) or the presentation was similar to that of BPC 157 rats(BPC 157 + L-NAME; BPC 157 + L-arginine; BPC 157 + L-NAME + L-arginine), except the defect did not change. Thereby at day 1 and 7, saline, L-NAME, L-arginine and L-NAME + L-arginine failed(defect was still open and large adhesions present). CONCLUSION The therapeutic effect was achieved with BPC 157 alone or in combination with L-NAME and L-arginine as it was able to consolidate the stimulating and inhibiting effects of the NO-system towards more effective healing recruiting vessels. | Domagoj Drmic Mariam Samara Tinka Vidovic Dominik Malekinusic Marko Antunovic Borna Vrdoljak Jelena Ruzman Marija Milkovic Perisa Katarina Horvat Pavlov Jerusha Jeyakumar Sven Seiwerth Predrag Sikiric | 2018 | World Journal of Gastroenterology2018，24，48： | 1 |
| 9 | Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine显示文摘AIM To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide(NO) system involvement.METHODS Male Wistar rats underwent superior anterior pancreaticoduodenal vein(SAPDV)-ligation and were treated with a bath at the ligated SAPDV site(BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 m L bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation(filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein(IAPDV) and superior mesenteric vein(SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO-and oxidative stress [malondialdehyde(MDA)]-levels in duodenum.RESULTS Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues.CONCLUSION BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, aneffect related to the NO system and reduction of free radical formation. | Fedor Amic Domagoj Drmic Zdenko Bilic Ivan Krezic Helena Zizek Marina Peklic Robert Klicek Alen Pajtak Enio Amic Tinka Vidovic Mislav Rakic Marija Milkovic Perisa Katarina Horvat Pavlov Antonio Kokot Ante Tvrdeic Alenka Boban Blagaic Mario Zovak Sven Seiwerth Predrag Sikiric | 2018 | World Journal of Gastroenterology2018，24，47： | 1 |
| 10 | Bowel adhesion and therapy with the stable gastric pentadecapeptide BPC 157,L-NAME and L-arginine in rats显示文摘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. | Lidija Berkopic Cesar Slaven Gojkovic Ivan Krezic Dominik Malekinusic Helena Zizek Lovorka Batelja Vuletic Andreja Petrovic Katarina Horvat Pavlov Domagoj Drmic Antonio Kokot Josipa Vlainic Sven Seiwerth Predrag Sikiric | 2020 | World Journal of Gastrointestinal Pharmacology and Therapeutics2020，11，5： | 0 |
| 11 | Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect显示文摘BACKGROUND Using rat stomach perforation as a prototypic direct lesion applied in cytoprotection research,we focused on the first demonstration of the severe occlusion/occlusion-like syndrome induced by stomach perforation.The revealed stomachinduced occlusion/occlusion-like syndrome corresponds to the previously described occlusion/occlusion-like syndromes in rats suffering multicausal pathology and shared severe vascular and multiorgan failure.This general point was particularly reviewed.As in all the described occlusion/occlusion-like syndromes with permanent occlusion of major vessels,peripheral and central,and other similar noxious procedures that severely affect endothelium function,the stable gastric pentadecapeptide BPC 157 was resolving therapy.AIM To reveal the stomach perforation-induced general occlusion/occlusion-like syndrome and BPC 157 therapy effect.METHODS The procedure included deeply anesthetized rats,complete calvariectomy,laparotomy at 15 min thereafter,and stomach perforation to rapidly induce vascular and multiorgan failure occlusion/occlusion-like syndrome.At 5 min post-perforation time,rats received therapy[BPC 157(10μg or 10 ng/kg)or saline(5 mL/kg,1 mL/rat)(controls)]into the perforated defect in the stomach).Sacrifice was at 15 min or 60 min post-perforation time.Assessment(gross and microscopy;volume)included:Brain swelling,peripheral vessels(azygos vein,superior mesenteric vein,portal vein,inferior caval vein)and heart,other organs lesions(i.e.,stomach,defect closing or widening);superior sagittal sinus,and peripherally the portal vein,inferior caval vein,and abdominal aorta blood pressures and clots;electrocardiograms;and bleeding time from the perforation(s).RESULTS BPC 157 beneficial effects accord with those noted before in the healing of the perforated defect(raised vessel presentation;less bleeding,defect contraction)and occlusion/occlusion-like syndromes counteraction.BPC 157 therapy(into the perforated defect),induced immediate shrinking and contraction of the whole stomach(unlike considerable enlargement by saline application).Accordingly,BPC 157 therapy induced direct blood delivery via the azygos vein,and attenuated/eliminated the intracranial(superior sagittal sinus),portal and caval hypertension,and aortal hypotension.Thrombosis,peripherally(inferior caval vein,portal vein,abdominal aorta)and centrally(superior sagittal sinus)BPC 157 therapy markedly reduced/annihilated.Severe lesions in the brain(swelling,hemorrhage),heart(congestion and arrhythmias),lung(hemorrhage and congestion),and marked congestion in the liver,kidney,and gastrointestinal tract were markedly reduced.CONCLUSION We revealed stomach perforation as a severe occlusion/occlusion-like syndrome,peripherally and centrally,and rapid counteraction by BPC 157 therapy.Thereby,further BPC 157 therapy may be warranted. | Luka Kalogjera Ivan Krezic Ivan Maria Smoday Hrvoje Vranes Helena Zizek Haidi Yago Katarina Oroz Vlasta Vukovic Ivana Kavelj Luka Novosel Slavica Zubcic Ivan Barisic Lidija Beketic Oreskovic Sanja Strbe Marko Sever Ivica Sjekavica Anita Skrtic Alenka Boban Blagaic Sven Seiwerth Predrag Sikiric | 2023 | World Journal of Gastroenterology2023，29，27： | 0 |
| 12 | Gastric pentadecapeptide BPC 157 in cytoprotection to resolve major vessel occlusion disturbances,ischemia-reperfusion injury following Pringle maneuver,and Budd-Chiari syndrome显示文摘The stable gastric pentadecapeptide BPC 157 counteracts various venous occlusion-induced syndromes.Summarized are all these arguments,in the Robert’s cytoprotection concept terms,to substantiate the resolution of different major vessel occlusion disturbances,in particular ischemia-reperfusion injury following the Pringle maneuver and Budd-Chiari syndrome,which was obtained by BPC 157 therapy.Conceptually,there is new point(bypassed occluded or ruptured vessel,the equation endothelium maintenance→epithelium maintenance=blood vessel recruitment and activation towards defect or bypassing vessel occlusion),the recruitment of collateral blood vessels to compensate for vessel occlusion and reestablish blood flow.In this paper,we summarize the evidence of the native cytoprotective gastric pentadecapeptide BPC 157,which is stable in the human gastric juice,is a membrane stabilizer and counteracts gut-leaky syndrome.As a particular target,it is distinctive from the standard peptide growth factors,with particular molecular pathways involved,controlling VEGF and NO pathways.In the early 1990s,BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection-organoprotection concept,epithelium,endothelium protection as previous theoretical/practical breakthrough in the 1980s,and brain-gut axis and gut-brain axis.As the time went on,with its reported effects,it is likely most useful theory practical implementation and justification.Meantime,several reviews suggest that BPC 157,which does not have a lethal dose(LD1),has profound cytoprotective activity,used to be demonstrated in ulcerative colitis and invented to multiple sclerosis trials.Likely,it may bring the theory to practical application,starting with the initial argument,no degradation in human gastric juice for more than 24 h,and thereby,the therapeutic effectiveness(including therapeutic per-oral regimen)and pleiotropic beneficial effects. | Predrag Sikiric Anita Skrtic Slaven Gojkovic Ivan Krezic Helena Zizek Eva Lovric Suncana Sikiric Mario Knezevic Sanja Strbe Marija Milavic Antonio Kokot Alenka Boban Blagaic Sven Seiwerth | 2022 | World Journal of Gastroenterology2022，28，1： | 0 |
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