Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats
We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and central...
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2022-01-01
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author | Ivan Barisic Diana Balenovic Mario Udovicic Darija Bardak Dean Strinic Josipa Vlainić Hrvoje Vranes Ivan Maria Smoday Ivan Krezic Marija Milavic Suncana Sikiric Sandra Uzun Gordana Zivanovic Posilovic Sanja Strbe Ivan Vukoja Eva Lovric Marin Lozic Marko Sever Martina Lovric Bencic Alenka Boban Blagaic Anita Skrtic Sven Seiwerth Predrag Sikiric |
author_facet | Ivan Barisic Diana Balenovic Mario Udovicic Darija Bardak Dean Strinic Josipa Vlainić Hrvoje Vranes Ivan Maria Smoday Ivan Krezic Marija Milavic Suncana Sikiric Sandra Uzun Gordana Zivanovic Posilovic Sanja Strbe Ivan Vukoja Eva Lovric Marin Lozic Marko Sever Martina Lovric Bencic Alenka Boban Blagaic Anita Skrtic Sven Seiwerth Predrag Sikiric |
author_sort | Ivan Barisic |
collection | DOAJ |
description | We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline-treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS-blocker, L-NAME. |
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spelling | doaj.art-970d5dba533b4325879bb3a2f3d9e6312023-11-23T18:52:57ZengMDPI AGBiomedicines2227-90592022-01-0110226510.3390/biomedicines10020265Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in RatsIvan Barisic0Diana Balenovic1Mario Udovicic2Darija Bardak3Dean Strinic4Josipa Vlainić5Hrvoje Vranes6Ivan Maria Smoday7Ivan Krezic8Marija Milavic9Suncana Sikiric10Sandra Uzun11Gordana Zivanovic Posilovic12Sanja Strbe13Ivan Vukoja14Eva Lovric15Marin Lozic16Marko Sever17Martina Lovric Bencic18Alenka Boban Blagaic19Anita Skrtic20Sven Seiwerth21Predrag Sikiric22Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Internal Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaLaboratory for Advanced Genomics, Division of Molecular Medicine, lnstitute Ruder Boskovic, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaClinic of Anaesthesiology, Reanimatology and Intensive Care Zagreb, University Hospital Centre Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaSchool of Medicine, University of Osijek, 31000 Osijek, CroatiaDepartment of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pediatric and Preventive Dentistry, School of Dental Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Internal Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, CroatiaWe revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline-treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS-blocker, L-NAME.https://www.mdpi.com/2227-9059/10/2/265pentadecapeptide BPC 157isoprenalineocclusion-like syndromemyocardial infarctionoxidative stressL-NAME |
spellingShingle | Ivan Barisic Diana Balenovic Mario Udovicic Darija Bardak Dean Strinic Josipa Vlainić Hrvoje Vranes Ivan Maria Smoday Ivan Krezic Marija Milavic Suncana Sikiric Sandra Uzun Gordana Zivanovic Posilovic Sanja Strbe Ivan Vukoja Eva Lovric Marin Lozic Marko Sever Martina Lovric Bencic Alenka Boban Blagaic Anita Skrtic Sven Seiwerth Predrag Sikiric Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats Biomedicines pentadecapeptide BPC 157 isoprenaline occlusion-like syndrome myocardial infarction oxidative stress L-NAME |
title | Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats |
title_full | Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats |
title_fullStr | Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats |
title_full_unstemmed | Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats |
title_short | Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats |
title_sort | stable gastric pentadecapeptide bpc 157 may counteract myocardial infarction induced by isoprenaline in rats |
topic | pentadecapeptide BPC 157 isoprenaline occlusion-like syndrome myocardial infarction oxidative stress L-NAME |
url | https://www.mdpi.com/2227-9059/10/2/265 |
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