Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 21, 2023; 29(27): 4289-4316
Published online Jul 21, 2023. doi: 10.3748/wjg.v29.i27.4289
Stomach perforation-induced general occlusion/occlusion-like syndrome and stable gastric pentadecapeptide BPC 157 therapy effect
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
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, Sanja Strbe, Marko Sever, Ivica Sjekavica, Alenka Boban Blagaic, Predrag Sikiric, Department of Pharmacology, School of Medicine, Zagreb 10000, Croatia
Lidija Beketic Oreskovic, Division of Oncology and Radiotherapy, University Hospital for Tumors, Sestre milosrdnice University Hospital Centre, Zagreb 10000, Croatia
Anita Skrtic, Sven Seiwerth, Department of Pathology, School of Medicine, Zagreb 10000, Croatia
Author contributions: Kalogjera L and Smoday IM contributed to conceptualization; Zizek H, Vukovic V, and Strbe S contributed to methodology; Sikiric P, Skrtic A, and Seiwerth S contributed to writing-original draft preparation, review, and editing; Boban Blagaic A and Beketic Oreskovic L contributed to visualization; Oroz K, Yago H, and Zubcic S contributed to investigation; Krezic I, Vranes H, and Barisic I contributed to formal analysis; Sjekavica I contributed to resources; Kavelj I, Novosel L, and Sever M contributed to validation.
Institutional animal care and use committee statement: This research was reviewed and approved by the Local Ethic Committee (Approval No. 380-59-10106-17-100/290).
Conflict-of-interest statement: Authors declare no conflict of interest.
Data sharing statement: The data that support the findings of this study are available from the corresponding author, upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Predrag Sikiric, MD, PhD, Full Professor, Department of Pharmacology, School of Medicine, 11 Salata, Zagreb 10000, Croatia. sikiric@mef.hr
Received: February 19, 2023
Peer-review started: February 19, 2023
First decision: May 23, 2023
Revised: June 1, 2023
Accepted: June 19, 2023
Article in press: June 19, 2023
Published online: July 21, 2023
Processing time: 143 Days and 21.1 Hours
Abstract
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 stomach-induced 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 (10 µg 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.

Keywords: Stomach perforation; General occlusion/occlusion-like syndrome; Stable gastric pentadecapeptide BPC 157; Cytoprotection; Therapy; Rats

Core Tip: Rats with perforated stomachs exhibited the rapidly emerging severe occlusion/occlusion-like syndrome, an innate general vascular and multiorgan failure, peripherally and centrally. The pentadecapeptide BPC 157 application into stomach defects was efficacious therapy. With an activated azygos vein-rescuing pathway, there was cause-consequence counteraction of lesions in the brain (swelling, hemorrhage), heart (congestion), lung (hemorrhage), and congestion in the liver, kidney, and gastrointestinal tract. Whole occlusion/occlusion-like syndrome, arrhythmias, blood pressure disturbances (intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension), major vessel failure, and widespread thrombosis, Virchow triad circumstances peripherally and centrally were all attenuated/eliminated by BPC 157 therapy.