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Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized r...

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Autores principales: Tepes, Marijan, Gojkovic, Slaven, Krezic, Ivan, Zizek, Helena, Vranes, Hrvoje, Madzar, Zrinko, Santak, Goran, Batelja, Lovorka, Milavic, Marija, Sikiric, Suncana, Kocman, Ivica, Simonji, Karol, Samara, Mariam, Knezevic, Mario, Barisic, Ivan, Lovric, Eva, Strbe, Sanja, Kokot, Antonio, Sjekavica, Ivica, Kolak, Toni, Skrtic, Anita, Seiwerth, Sven, Boban Blagaic, Alenka, Sikiric, Predrag
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710746/
https://www.ncbi.nlm.nih.gov/pubmed/34966273
http://dx.doi.org/10.3389/fphar.2021.718147
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author Tepes, Marijan
Gojkovic, Slaven
Krezic, Ivan
Zizek, Helena
Vranes, Hrvoje
Madzar, Zrinko
Santak, Goran
Batelja, Lovorka
Milavic, Marija
Sikiric, Suncana
Kocman, Ivica
Simonji, Karol
Samara, Mariam
Knezevic, Mario
Barisic, Ivan
Lovric, Eva
Strbe, Sanja
Kokot, Antonio
Sjekavica, Ivica
Kolak, Toni
Skrtic, Anita
Seiwerth, Sven
Boban Blagaic, Alenka
Sikiric, Predrag
author_facet Tepes, Marijan
Gojkovic, Slaven
Krezic, Ivan
Zizek, Helena
Vranes, Hrvoje
Madzar, Zrinko
Santak, Goran
Batelja, Lovorka
Milavic, Marija
Sikiric, Suncana
Kocman, Ivica
Simonji, Karol
Samara, Mariam
Knezevic, Mario
Barisic, Ivan
Lovric, Eva
Strbe, Sanja
Kokot, Antonio
Sjekavica, Ivica
Kolak, Toni
Skrtic, Anita
Seiwerth, Sven
Boban Blagaic, Alenka
Sikiric, Predrag
author_sort Tepes, Marijan
collection PubMed
description Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior–superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.
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spelling pubmed-87107462021-12-28 Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats Tepes, Marijan Gojkovic, Slaven Krezic, Ivan Zizek, Helena Vranes, Hrvoje Madzar, Zrinko Santak, Goran Batelja, Lovorka Milavic, Marija Sikiric, Suncana Kocman, Ivica Simonji, Karol Samara, Mariam Knezevic, Mario Barisic, Ivan Lovric, Eva Strbe, Sanja Kokot, Antonio Sjekavica, Ivica Kolak, Toni Skrtic, Anita Seiwerth, Sven Boban Blagaic, Alenka Sikiric, Predrag Front Pharmacol Pharmacology Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior–superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome. Frontiers Media S.A. 2021-12-13 /pmc/articles/PMC8710746/ /pubmed/34966273 http://dx.doi.org/10.3389/fphar.2021.718147 Text en Copyright © 2021 Tepes, Gojkovic, Krezic, Zizek, Vranes, Madzar, Santak, Batelja, Milavic, Sikiric, Kocman, Simonji, Samara, Knezevic, Barisic, Lovric, Strbe, Kokot, Sjekavica, Kolak, Skrtic, Seiwerth, Boban Blagaic and Sikiric. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Tepes, Marijan
Gojkovic, Slaven
Krezic, Ivan
Zizek, Helena
Vranes, Hrvoje
Madzar, Zrinko
Santak, Goran
Batelja, Lovorka
Milavic, Marija
Sikiric, Suncana
Kocman, Ivica
Simonji, Karol
Samara, Mariam
Knezevic, Mario
Barisic, Ivan
Lovric, Eva
Strbe, Sanja
Kokot, Antonio
Sjekavica, Ivica
Kolak, Toni
Skrtic, Anita
Seiwerth, Sven
Boban Blagaic, Alenka
Sikiric, Predrag
Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title_full Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title_fullStr Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title_full_unstemmed Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title_short Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats
title_sort stable gastric pentadecapeptide bpc 157 therapy for primary abdominal compartment syndrome in rats
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710746/
https://www.ncbi.nlm.nih.gov/pubmed/34966273
http://dx.doi.org/10.3389/fphar.2021.718147
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