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

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...

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Published in:	PloS one 2015-04, Vol.10 (4), p.e0123454-e0123454
Main Authors:	Stupnisek, Mirjana, Kokot, Antonio, Drmic, Domagoj, Hrelec Patrlj, Masa, Zenko Sever, Anita, Kolenc, Danijela, Radic, Bozo, Suran, Jelena, Bojic, Davor, Vcev, Aleksandar, Seiwerth, Sven, Sikiric, Predrag
Format:	Article
Language:	eng
Subjects:	Amputation Animals Anticoagulants Anticoagulants - pharmacology Arginine Bleeding Blood platelets Drug dosages Drug Evaluation, Preclinical Endothelium Growth factors Hemorrhage Hemorrhage - chemically induced Hemorrhage - drug therapy Hemostasis Hemostatics Heparin Heparin - pharmacology Male Medicine NG-Nitroarginine Methyl Ester Nitric oxide Nitric-oxide synthase Pathology Peptide Fragments - pharmacology Peptide Fragments - therapeutic use Peptides Pharmacology Proteins - pharmacology Proteins - therapeutic use Rats, Wistar Rodents Substrates Tails Thrombocytopenia Thrombocytopenia - chemically induced Thrombocytopenia - drug therapy Warfarin Warfarin - pharmacology Wound healing
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Summary:	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. 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. 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. 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.
ISSN:	1932-6203 1932-6203