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Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157.

J. Vukojević,M. Siroglavić,K. Kašnik,T. Kralj,D. Stanćić,A. Kokot,D. Kolarić,D. Drmic,A. Z. Sever,I. Barišić,J. Šuran,D. Bojic,M. H. Patrlj,I. Sjekavica,K. Pavlov,Tinka Vidović,J. Vlainić,M. Stupnišek,S. Seiwerth,P. Sikiric

Published 2018 in Vascular pharmacology

ABSTRACT

Rat inferior caval vein (ICV) ligation (up to the right ovarian vein (ROV)) commonly represents a recapitulation of Virchow: with ligation leading to vessel injury, stasis, thrombosis and hemodynamic changes. We revealed that BPC 157's therapy collectively attenuated or counteracted all these events and the full syndrome. METHODS We applied BPC 157 (10 μg, 10 ng/kg) as an early regimen or as a delayed therapy. Assessment includes gross assessment by microcamera; microscopy, venography, bleeding, blood pressure, ECG, thermography, MDA and NO-level in plasma and ICV, and gene expression. RESULTS Direct vein injury, thrombosis, thrombocytopenia, prolonged bleeding were all counteracted. Also, rapid presentation of collaterals and redistribution of otherwise trapped blood volume (bypassing through the left ovarian vein (LOV) and other veins), with venous hypertension, arterial hypotension and tachycardia counteraction were shown. BPC 157-rats presented raised plasma NO-values, but normal MDA-values; in ICV tissue reverted low NO-values and counteracted increased MDA-levels. Altered expression of EGR, NOS, SRF, VEGFR and KRAS in ICV, ROV and LOV revealed increased or decreased levels, while some genes continuously remained unchanged. CONCLUSION As a new insight, BPC 157 application largely attenuated or even completely eliminated all consequences of ICV ligation in rats.

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