Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

Abstract

BACKGROUND:

BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin.

METHODS:

Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination.

RESULTS:

After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia.

CONCLUSIONS:

L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

• Authors: Mirjana Stupnisek, Antonio Kokot, Domagoj Drmic, Masa Hrelec Patrlj, Anita Zenko Sever, Danijela Kolenc, Bozo Radic, Jelena Suran, Davor Bojic, Aleksandar Vcev, Sven Seiwerth, Predrag Sikiric
• Journal: PloS one (PLoS One) Vol. 10 Issue 4 Pg. e0123454 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25897838 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticoagulants
• Peptide Fragments
• Proteins
• Warfarin
• BPC 157
• Heparin
• Arginine
• NG-Nitroarginine Methyl Ester

Topics

• Amputation, Surgical
• Animals
• Anticoagulants (pharmacology)
• Arginine
• Drug Evaluation, Preclinical
• Hemorrhage (chemically induced, drug therapy)
• Hemostasis
• Heparin (pharmacology)
• Male
• NG-Nitroarginine Methyl Ester
• Peptide Fragments (pharmacology, therapeutic use)
• Proteins (pharmacology, therapeutic use)
• Rats, Wistar
• Thrombocytopenia (chemically induced, drug therapy)
• Warfarin (pharmacology)