Stable Gastric Pentadecapeptide BPC 157 Therapy: Effect on Reperfusion Following Maintained Intra-Abdominal Hypertension (Grade III and IV) in Rats

Author:

Tepes Marijan123,Krezic Ivan1,Vranes Hrvoje1ORCID,Smoday Ivan Maria1,Kalogjera Luka1ORCID,Zizek Helena1,Vukovic Vlasta1ORCID,Oroz Katarina1,Kovac Katarina Kasnik1,Madzar Zrinko1,Rakic Mislav4,Miskic Blazenka2ORCID,Sikiric Suncana5,Barisic Ivan1,Strbe Sanja1,Antunovic Marko1,Novosel Luka1,Kavelj Ivana1,Vlainic Josipa6,Dobric Ivan7,Staresinic Mario7,Skrtic Anita5ORCID,Seiwerth Sven5,Blagaic Alenka Boban1,Sikiric Predrag1ORCID

Affiliation:

1. Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

2. Department of Clinical Medicine, Faculty of Dental Medicine and Health Osijek, 31000 Osijek, Croatia

3. PhD Program Translational Research in Biomedicine-TRIBE, School of Medicine, University of Split, 21000 Split, Croatia

4. Department of Abdominal Surgery, Clinical Hospital Dubrava, 10040 Zagreb, Croatia

5. Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

6. Laboratory for Advanced Genomics, Division of Molecular Medicine, Institute Ruder Boskovic, 10000 Zagreb, Croatia

7. Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia

Abstract

Given in reperfusion, the use of stable gastric pentadecapeptide BPC 157 is an effective therapy in rats. It strongly counteracted, as a whole, decompression/reperfusion-induced occlusion/occlusion-like syndrome following the worst circumstances of acute abdominal compartment and intra-abdominal hypertension, grade III and grade IV, as well as compression/ischemia-occlusion/occlusion-like syndrome. Before decompression (calvariectomy, laparotomy), rats had long-lasting severe intra-abdominal hypertension, grade III (25 mmHg/60 min) (i) and grade IV (30 mmHg/30 min; 40 mmHg/30 min) (ii/iii), and severe occlusion/occlusion-like syndrome. Further worsening was caused by reperfusion for 60 min (i) or 30 min (ii/iii). Severe vascular and multiorgan failure (brain, heart, liver, kidney, and gastrointestinal lesions), widespread thrombosis (peripherally and centrally) severe arrhythmias, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension were aggravated. Contrarily, BPC 157 therapy (10 µg/kg, 10 ng/kg sc) given at 3 min reperfusion times eliminated/attenuated venous hypertension (intracranial (superior sagittal sinus), portal, and caval) and aortal hypotension and counteracted the increases in organ lesions and malondialdehyde values (blood ˃ heart, lungs, liver, kidney ˃ brain, gastrointestinal tract). Vascular recovery promptly occurred (i.e., congested inferior caval and superior mesenteric veins reversed to the normal vessel presentation, the collapsed azygos vein reversed to a fully functioning state, the inferior caval vein–superior caval vein shunt was recovered, and direct blood delivery returned). BPC 157 therapy almost annihilated thrombosis and hemorrhage (i.e., intracerebral hemorrhage) as proof of the counteracted general stasis and Virchow triad circumstances and reorganized blood flow. In conclusion, decompression/reperfusion-induced occlusion/occlusion-like syndrome counteracted by BPC 157 therapy in rats is likely for translation in patients. It is noteworthy that by rapidly counteracting the reperfusion course, it also reverses previous ischemia-course lesions, thus inducing complete recovery.

Funder

University of Zagreb

Publisher

MDPI AG

Subject

Drug Discovery,Pharmaceutical Science,Molecular Medicine

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