Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

doi:10.4291/wjgp.v11.i1.1

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World Journal of Gastrointestinal Pathophysiology

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Basic Study

World J Gastrointest Pathophysiol. Mar 13, 2020; 11(1): 1-19
Published online Mar 13, 2020. doi: 10.4291/wjgp.v11.i1.1

Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

Slaven Gojkovic, Ivan Krezic, Borna Vrdoljak, Dominik Malekinusic, Ivan Barisic, Andreja Petrovic, Katarina Horvat Pavlov, Marijan Kolovrat, Antonija Duzel, Mario Knezevic, Katarina Kasnik Kovac, Domagoj Drmic, Lovorka Batelja Vuletic, Antonio Kokot, Alenka Boban Blagaic, Sven Seiwerth, Predrag Sikiric

Author contributions: Gojkovic S, Krezic I, Vrdoljak B, Malekinusic D, Barisic I, Petrovic A, Horvat Pavlov K, Kolovrat M, Duzel A, Knezevic M, Kasnik Kovac K, Drmic D, Batelja Vuletic L, Kokot A, Boban Blagaic A, Seiwerth S and Sikiric P performed experiments; Gojkovic S, Krezic I, Vrdoljak B, Malekinusic D, Barisic I, Petrovic A, Horvat Pavlov K, Kolovrat M, Duzel A, Knezevic M, Kasnik Kovac K, Drmic D, Batelja Vuletic L, Kokot A, Boban Blagaic A, Seiwerth S and Sikiric P analysed data; Seiwerth S and Sikiric P contributed reagents and analytic tools; Gojkovic S, Drmic D, Seiwerth S and Sikiric P wrote the manuscript.

Institutional review board statement: The study was reviewed and approved by the Department of Veterinary, Ministry of Agriculture, Republic of Croatia, No: UP/I 322-01/07-01/210.

Institutional animal care and use committee statement: Male Albino Wistar, body weight 200 g, 12 weeks old, randomly assigned, used in all of the experiments, 6 rats/group/interval, approved by local Ethic Committee.

Conflict-of-interest statement: The authors state that they have no conflicts of interest.

Data sharing statement: No additional data are available.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Corresponding author: Predrag Sikiric, MD, PhD, Professor, Department of Pharmacology, School of Medicine, University of Zagreb, Salata 11, POB 916, Zagreb 10000, Croatia. sikiric@mef.hr

Received: October 7, 2019
Peer-review started: October 7, 2019
First decision: November 27, 2019
Revised: December 20, 2019
Accepted: January 19, 2020
Article in press: January 19, 2020
Published online: March 13, 2020
Processing time: 157 Days and 14 Hours

Core Tip

Core tip: To demonstrate that pentadecapeptide BPC 157 can resolve Budd Chiari syndrome in rats, we provided gross, microscopy, nitric oxide-, malondialdehyde-liver levels, serum enzymes, electrocardiogram, portal, caval hypertension, aortal hypotension, thrombosis, hepatomegaly, splenomegaly and venography assessments. BPC 157 counteracts increased P wave amplitude, tachycardia and ST-elevation (i.e., right heart failure; acute thrombotic coronary occlusion). Bypassing pathway (inferior caval vein-azygos (hemiazygos) vein-superior caval vein and portocaval shunt) rapidly appears. Even with the severe caval ˃ portal hypertension, BPC 157 counteracts portal and caval hypertension and aortal hypotension. BPC 157 counteracts refractory ascites. Portal vein tributaries, inferior caval vein, hepatic and coronary arteries thrombosis was counteracted. In addition, there are counteracted severe lung pathology, liver, intestine hemorrhagic lesion, increased liver and spleen weight. During ligation-period, nitric oxide- and malondialdehyde-level in liver remained within normal healthy values, and increased serum enzymes markedly lessened. In conclusion, BPC 157 counteracts Budd Chiari syndrome in rats.