The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation

Sikirić, Predrag; Šeparović, Jadranka; Anić, Tomislav; Buljat, Gojko; Mikus, Darko; Seiwerth, Sven; Grabarević, Željko; Stančić-Rokotov, Dinko; Pigac, Biserka; Hanzevacki, Miroslav; Marović, Anton; Rucman, Rudolf; Petek, Marijan; Zoricic, Ivan; Ziger, Tomislav; Aralica, Gorana; Konjevoda, Paško; Prkačin, Ingrid; Gjurašin, Miroslav; Miklić, Pavle; Artuković, Branka; Tišljar, Marina; Bratulić, Mirna; Miše, Stjepan; Rotkvić, Ivo

doi:10.1016/s0928-4257(99)00123-0

Cited by 44 publications

(43 citation statements)

References 24 publications

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“…Based on the close similarity of the determination of NO-synthesis in gastric and other tissues (39), this pentadecapeptide would probably have a similar activity in other organs as well, which is relevant for both the skin and mucosa healing. In support of this, BPC 157 has a strong angiogenic effect (12,35,49) [i.e., angiogenesis is an essential component of ulcer healing since it assures delivery of oxygen and nutrients to the healing site (26)]. Likewise, BPC 157 counteracted endothelin over-expression (50).…”

Section: Discussionmentioning

confidence: 96%

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

et al. 2008

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Abstract. We focused on the therapeutic effect of the stable gastric pentadecapeptide BPC 157 and how its action is related to nitric oxide (NO) in persistent colocutaneous fistula in rats (at 5 cm from anus, colon defect of 5 mm, skin defect of 5 mm); this peptide has been shown to be safe in clinical trials for inflammatory bowel disease (PL14736) and safe for intestinal anstomosis therapy. BPC 157 (10 μg / kg, 10 ng / kg) was applied i) in drinking water until the animals were sacrificed at post-operative day 1, 3, 5, 7, 14, 21, and 28; or ii) once daily intraperitoneally (first application 30 min following surgery, last 24 h before sacrifice) alone or with N G -nitro-L-arginine methyl ester (L-NAME) (5 mg / kg), L-arginine (200 mg/ kg), and their combinations. Sulphasalazine (50 mg / kg) and 6-α-methylprednisolone (1 mg / kg) were given once daily intraperitoneally. BPC 157 accelerated parenterally or perorally the healing of colonic and skin defect, leading to the suitable closure of the fistula, macro / microscopically, biomechanically, and functionally (larger water volume sustained without fistula leaking). L-NAME aggravated the healing failure of colocutaneous fistulas, skin, and colon wounds (L-NAME groups). L-Arginine was effective only with blunted NO generation (L-NAME + L-arginine groups) but not without (L-arginine groups). All of the BPC 157 beneficial effects remained unchanged with blunted NO-generation (L-NAME + BPC 157 groups) and with NO substrate (L-arginine + BPC 157 groups) as well as L-NAME and L-arginine co-administration (L-NAME + L-arginine + BPC 157 groups). Sulphasalazine was only moderately effective, and corticosteroid even had an aggravating effect.

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Section: Discussionmentioning

confidence: 96%

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

et al. 2008

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“…In extension of transected tendon healing 1,2 and other wound healing, 1,2,5,7 -9 gastric pentadecapeptide BPC 157 likely controls functions of collagen fragments 1,7,8 (here, abundant collagen fibers with longitudinal orientation as in transected tendon healing 1 ), has an angiogenic effect 1,7,22 (here, an increase of blood vessels well formed and longitudinally oriented, with desmin staining prominent positivity present throughout the active border of the transection, unlike controls) and directly protects endothelium and modulates NOsynthesis. 10 These may directly affect the healing repair of connective tissues, 1 presenting NO-system directly related to skeletal muscle and muscle injuries, and considering essential role of NO in healing 23 as an ordered multistage process.…”

Section: Discussionmentioning

confidence: 99%

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157

Silva

Petrović

Novinščak

et al. 2006

Journal Orthopaedic Research

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159

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ABSTRACT:We report complete transection of major muscle and the systemic peptide treatment that induces healing of quadriceps muscle promptly and then maintains the healing with functional restoration. Initially, stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736 Pliva, Croatia; in trials for inflammatory bowel disease; wound treatment; no toxicity reported; effective alone without carrier) also superiorly accelerates the healing of transected Achilles tendon. Regularly, quadriceps muscle completely transected transversely 1.0 cm proximal to patella presents a definitive defect that cannot be compensated in rat. BPC 157 (10 mg, 10 ng, 10 pg/kg) is given intraperitoneally, once daily; the first application 30 min posttransection, the final 24 h before sacrifice. It consistently improves muscle healing throughout the whole 72-day period. Improved are: (i) biomechanic (load of failure increased); (ii) function (walking recovery and extensor postural thrust/motor function index returned toward normal healthy values); (iii) microscopy/immunochemistry [i.e., mostly muscle fibers connect muscle segments; absent gap; significant desmin positivity for ongoing regeneration of muscle; larger myofibril diameters on both sides, distal and proximal (normal healthy rat-values reached)]; (iv) macroscopic presentation (stumps connected; subsequently, atrophy markedly attenuated; finally, presentation close to normal noninjured muscle, no postsurgery leg contracture). Thus, posttransection healing-consistently improved-may suggest this peptide therapeutic application in muscle disorders. ß

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“…Generally, after Achilles tendon detachment, BPC 157-treated rats show more blood vessels and dilated capillary beds at injury site in the early healing period (day 4). BPC 157 has angiogenic potential, 6,21,22 directly protects endothelium, 22 counteracts endothelin overproduction, 20 and modulates NO synthesis, and NO system function, 14 and is substantially involved in tendon and bone injury and healing [27][28][29] [i.e., BPC 157 opposes both Larginine-NO synthesis overexpression, and NO synthesis inhibitor N G -nitro-L-arginine methylester (L-NAME) harmful effect also seen in tendon and bone injuries].…”

Section: Discussionmentioning

confidence: 99%

Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon‐to‐Bone Healing and Opposed Corticosteroid Aggravation

Krivić

Anić

Seiwerth

et al. 2006

Journal Orthopaedic Research

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119

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Stable gastric pentadecapeptide BPC 157 (BPC 157, as an antiulcer agent in clinical trials for inflammatory bowel disease; PLD-116, PL 14736, Pliva, no toxicity reported) alone (without carrier) ameliorates healing of tendon and bone, respectively, as well as other tissues. Thereby, we focus on Achilles tendon-to-bone healing: tendon to bone could not be healed spontaneously, but it was recovered by this peptide. After the rat's Achilles tendon was sharply transected from calcaneal bone, agents [BPC 157 (10 microg, 10 ng, 10 pg), 6alpha-methylprednisolone (1 mg), 0.9% NaCl (5 mL)] were given alone or in combination [/kg body weight (b.w.) intraperitoneally, once time daily, first 30-min after surgery, last 24 h before analysis]. Tested at days 1, 4, 7, 10, 14, and 21 after Achilles detachment, BPC 157 improves healing functionally [Achilles functional index (AFI) values substantially increased], biomechanically (load to failure, stiffness, and Young elasticity modulus significantly increased), macro/microscopically, immunohistochemistry (better organization of collagen fibers, and advanced vascular appearance, more collagen type I). 6alpha-Methylprednisolone consistently aggravates the healing, while BPC 157 substantially reduces 6alpha-methylprednisolone healing aggravation. Thus, direct tendon-to-bone healing using stabile nontoxic peptide BPC 157 without a carrier might successfully exchange the present reconstructive surgical methods.

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The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation

Cited by 44 publications

References 24 publications

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

Pentadecapeptide BPC 157, in Clinical Trials as a Therapy for Inflammatory Bowel Disease (PL14736), Is Effective in the Healing of Colocutaneous Fistulas in Rats: Role of the Nitric Oxide-System

Effective therapy of transected quadriceps muscle in rat: Gastric pentadecapeptide BPC 157

Achilles Detachment in Rat and Stable Gastric Pentadecapeptide BPC 157: Promoted Tendon‐to‐Bone Healing and Opposed Corticosteroid Aggravation

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