In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro

Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsio...

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Main Authors: Marin Lozic, Vasilije Stambolija, Ivan Krezic, Aleksandra Dugandzic, Gordana Zivanovic-Posilovic, Slaven Gojkovic, Josip Kovacevic, Luka Vrdoljak, Ivan Mirkovic, Antonio Kokot, Andreja Petrovic, Katarina Horvat Pavlov, Domagoj Drmic, Jelena Suran, Alenka Boban Blagaic, Sven Seiwerth, Predrag Sikiric
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Emergency Medicine International
Online Access:http://dx.doi.org/10.1155/2020/6805354
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author Marin Lozic
Vasilije Stambolija
Ivan Krezic
Aleksandra Dugandzic
Gordana Zivanovic-Posilovic
Slaven Gojkovic
Josip Kovacevic
Luka Vrdoljak
Ivan Mirkovic
Antonio Kokot
Andreja Petrovic
Katarina Horvat Pavlov
Domagoj Drmic
Jelena Suran
Alenka Boban Blagaic
Sven Seiwerth
Predrag Sikiric
author_facet Marin Lozic
Vasilije Stambolija
Ivan Krezic
Aleksandra Dugandzic
Gordana Zivanovic-Posilovic
Slaven Gojkovic
Josip Kovacevic
Luka Vrdoljak
Ivan Mirkovic
Antonio Kokot
Andreja Petrovic
Katarina Horvat Pavlov
Domagoj Drmic
Jelena Suran
Alenka Boban Blagaic
Sven Seiwerth
Predrag Sikiric
author_sort Marin Lozic
collection DOAJ
description Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other’s response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.
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spelling doaj-art-a0b7b5f552e24aefaad33ab6fca255f62025-02-03T05:49:52ZengWileyEmergency Medicine International2090-28402090-28592020-01-01202010.1155/2020/68053546805354In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In VitroMarin Lozic0Vasilije Stambolija1Ivan Krezic2Aleksandra Dugandzic3Gordana Zivanovic-Posilovic4Slaven Gojkovic5Josip Kovacevic6Luka Vrdoljak7Ivan Mirkovic8Antonio Kokot9Andreja Petrovic10Katarina Horvat Pavlov11Domagoj Drmic12Jelena Suran13Alenka Boban Blagaic14Sven Seiwerth15Predrag Sikiric16Department of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaDepartment of Pharmacology, School of Medicine, Medical Faculty, University of Zagreb, Salata 11, P.O. Box 916, 10000 Zagreb, CroatiaRecently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other’s response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.http://dx.doi.org/10.1155/2020/6805354
spellingShingle Marin Lozic
Vasilije Stambolija
Ivan Krezic
Aleksandra Dugandzic
Gordana Zivanovic-Posilovic
Slaven Gojkovic
Josip Kovacevic
Luka Vrdoljak
Ivan Mirkovic
Antonio Kokot
Andreja Petrovic
Katarina Horvat Pavlov
Domagoj Drmic
Jelena Suran
Alenka Boban Blagaic
Sven Seiwerth
Predrag Sikiric
In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
Emergency Medicine International
title In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
title_full In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
title_fullStr In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
title_full_unstemmed In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
title_short In relation to NO-System, Stable Pentadecapeptide BPC 157 Counteracts Lidocaine-Induced Adverse Effects in Rats and Depolarisation In Vitro
title_sort in relation to no system stable pentadecapeptide bpc 157 counteracts lidocaine induced adverse effects in rats and depolarisation in vitro
url http://dx.doi.org/10.1155/2020/6805354
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