The influence of a novel pentadecapeptide, BPC 157, on NG-nitro-l-arginine methylester and l-arginine effects on stomach mucosa integrity and blood pressure

Sikirić, Predrag; Seiwerth, Sven; Grabarević, Ž.; Rucman, Rudolf; Petek, Marijan; Jagić, Vjekoslav; Turković, Branko; I, Rotkvić; Miše, Stjepan; Zoricic, Ivan; Konjevoda, Paško; Perović, Darko; Jurina, Ljubica; Šeparović, Jadranka; Hanzevacki, Miroslav; Artuković, Branka; Bratulić, Mirna; Tišljar, Marina; Gjurašin, Miroslav; Miklić, Pavle; Stančić-Rokotov, Dinko; Slobodnjak, Zoran; Jelovac, Nikola; Marović, Anton

doi:10.1016/s0014-2999(97)01033-9

Cited by 122 publications

(209 citation statements)

References 21 publications

Supporting

Mentioning

200

Contrasting

Order By: Relevance

“…Here, unlike effects of standard growth factors with carrier(s) 14,15 (thereby, peptide þ carrier(s)-complex with considerable methodological/activity dilemmas 15 ), these special pentadecapeptide BPC 157 characteristics [i.e., its high stability (in human gastric juice 17 ), use without carrier [1][2][3][4][5][6][7][8][9][10][11][12]18,19 ] permit its functional, biomechanical, macroscopic, and microscopic effects [1][2][3][4][5][6][7][8][9][10][11][12]18,19 and exemplified mechanism(s) to be unmistakably attributed.…”

Section: Discussionmentioning

confidence: 99%

“…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. Occurring proliferation and migration of many cell types, reduced levels of inflammatory markers (MPO, LTB4, TXB2), collagen synthesis, angiogenesis, production of granulation tissue have been coined with pentadecapeptide BPC 157.…”

Section: Discussionmentioning

confidence: 99%

“…Sham procedure used skin lesion only, and nonoperated healthy rats present an additional control (since not different, these data are not specifically shown). Medication (pentadecapeptide BPC 157 [manufactured by Diagen, Ljubljana, Slovenia, [1][2][3][4][5][6][7][8][9][10][11][12]18,19 GEPPPGKPADDAGLV, M.W. 1419, partial sequence of human gastric juice protein BPC, peptide with 99% (HPLC), freely soluble in water at pH 7.0 and in saline] dissolved in saline (10 mg, 10 ng, or 10 pg/kg b.w.)…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, an advantageously accelerated healing of transected Achilles tendon in rat 1,2 with a stable peptide, effective alone without carrier, gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419, PL-10, PLD-116, PL 14736, Pliva, Croatia, in clinical trials for inflammatory bowel disease, 3 ulcer, and wound treatment, [1][2][3][4][5][6][7][8][9][10][11][12] no toxicity reported 3 ) could resolve unclear systemic peptide treatment of major muscle injury. Of note, like in tendon-healing, 13 muscle-healing with standard peptide (in)efficiency, 14 uncertain delivery, 15 besides carrier addition, 13,15 unable to deliver healing to an injured muscle, essentially restraints the systemic peptide treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Mostly limited to direct local administration, standard peptide growth factors 14 elicit no full muscle recovery, but rather scar tissue accumulation, 14 even confronted with less severe injuries [besides, wound healing by transforming growth factor (TGF)-b given with carrier 16 contrasts with muscle healing attempts with antifibrotic agents, TGF-b1 inhibitors 14 ]. On the contrary, muscle-healing, not restricted to direct local peptide application, likely could be achieved with BPC 157: a stable agent (i.e., in otherwise highly degradating media, like in human gastric juice more than 24 h, unlike standard growth factors degrading within minutes 17 ) advantageously effective alone, given systemically, without carrier, [1][2][3][4][5][6][7][8][9][10][11][12]18,19 with woundhealing treatment 1,2,5,7 -9 presents posttransection healing promptly and then maintains the healing along with full function restoration, 1 even tendonto-bone healing, 2 despite hypocellular, hypovascular, hyponeural conditions. 1 Besides, the potential upregulation of the growth factors, and other local factors, acting to mediate the growth and repair, was suggested (i.e., deep skin burns 7 ), and it acts even without a major source of growth factors, such as salivary gland.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Silva

Petrović

Novinščak

et al. 2006

Journal Orthopaedic Research

Self Cite

159

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Silva

Petrović

Novinščak

et al. 2006

Journal Orthopaedic Research

Self Cite

159

View full text Add to dashboard Cite

show abstract

The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background and purpose We focused on the, yet undescribed, therapy effect of the stable gastric pentadecapeptide BPC 157 in hippocampal ischemia/reperfusion injuries, after bilateral clamping of the common carotid arteries in rats. The background is the proven therapy effect of BPC 157 in ischemia/reperfusion injuries in different tissues. Furthermore, there is the subsequent oxidative stress counteraction, particularly when given during reperfusion. The recovering effect it has on occluded vessels, results with activation of the alternative pathways, bypassing the occlusion in deep vein thrombosis. Finally, the BPC 157 therapy benefits with its proposed role as a novel mediator of Roberts’ cytoprotection and bidirectional effects in the gut‐brain axis. Materials and Methods Male Wistar rats underwent bilateral clamping of the common carotid arteries for a 20‐min period. At 30 s thereafter, we applied medication (BPC 157 10 µg/kg; or saline) as a 1 ml bath directly to the operated area, that is, trigonum caroticum. We documented, in reperfusion, the resolution of the neuronal damages sustained in the brain, resolution of the damages reflected in memory, locomotion, and coordination disturbances, with the presentation of the particular genes expression in hippocampal tissues. Results In the operated rats, at 24 and 72 hr of the reperfusion, the therapy counteracted both early and delayed neural hippocampal damage, achieving full functional recovery (Morris water maze test, inclined beam‐walking test, lateral push test). mRNA expression studies at 1 and 24 hr, provided strongly elevated ( Egr1, Akt1, Kras, Src, Foxo, Srf, Vegfr2, Nos3, and Nos1 ) and decreased ( Nos2, Nfkb ) gene expression ( Mapk1 not activated), as a way how BPC 157 may act. Conclusion Together, these findings suggest that these beneficial BPC 157 effects may provide a novel therapeutic solution for stroke.

show abstract

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

Self Cite

119

View full text Add to dashboard Cite

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.

show abstract

The influence of a novel pentadecapeptide, BPC 157, on NG-nitro-l-arginine methylester and l-arginine effects on stomach mucosa integrity and blood pressure

Cited by 122 publications

References 21 publications

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

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

The effect of pentadecapeptide BPC 157 on hippocampal ischemia/reperfusion injuries in rats

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

Contact Info

Product

Resources

About