title: 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.affiliation: Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stupnisek
authors.affiliation: Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Antonio
authors.initials: A
authors.lastname: Kokot
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Masa
authors.initials: M
authors.lastname: Hrelec Patrlj
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Zenko Sever
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Danijela
authors.initials: D
authors.lastname: Kolenc
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Suran
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Bojic
authors.affiliation: Faculty of Medicine, J.J. Strossmayer University of Osijek, Osijek, Croatia.
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Vcev
authors.affiliation: Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.affiliation: Department of Pharmacology, School of Medicine, University of Zagreb, Zagreb, Croatia.
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000671:Amputation, Surgical; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine; D004353:Drug Evaluation, Preclinical; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy*; D006487:Hemostasis; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D011506:Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D017208:Rats, Wistar; D013921:Thrombocytopenia / Q000139:chemically induced / Q000188:drug therapy*; D014859:Warfarin / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D010446:Peptide Fragments; D011506:Proteins; D014859:Warfarin; C083833:BPC 157; D006493:Heparin; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester