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

Tepeš, Marijan; Krezić, Ivan; Vraneš, Hrvoje; Smoday, Ivan Maria; Kalogjera, Luka; Žižek, Helena; Vuković, Vlasta; Oroz, Katarina; Kovač, Katarina Kašnik; Madžar, Zrinko; Rakić, Mislav; Miškić, Blaženka; Sikirić, Sunčana; Barišić, Ivan; Štrbe, Sanja; Antunović, Marko; Novosel, Luka; Kavelj, Ivana; Vlainić, Josipa; Dobrić, Ivan; Starešinić, Mario; Škrtić, Anita; Seiwerth, Sven; Blagaić, Alenka Boban; Sikirić, Predrag (2023) Stable Gastric Pentadecapeptide BPC 157 Therapy: Effect on Reperfusion Following Maintained Intra-Abdominal Hypertension (Grade III and IV) in Rats. Pharmaceuticals, 16 (11). ISSN 1424-8247

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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.

Item Type:	Article
Uncontrolled Keywords:	prime acute abdominal compartment; occlusion/occlusion-like syndrome; reperfusion; stable gastric pentadecapeptide BPC 157 therapy
Subjects:	BIOMEDICINE AND HEALTHCARE > Clinical Medical Sciences > Internal Medicine
Divisions:	Division of Molecular Medicine
Depositing User:	Lorena Palameta
Date Deposited:	09 Sep 2024 08:21
URI:	http://fulir.irb.hr/id/eprint/9072
DOI:	10.3390/ph16111554

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