Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157

Vukojević, Jakša; Siroglavić, Marko; Kasnik, Katarina; Kralj, Tamara; Stancic, Duje; Kokot, Antonio; Kolarić, Darko; Drmic, Domagoj; Sever, Anita Zenko; Barišić, Ivan; Šuran, Jelena; Bojić, Davor; Patrlj, Masa Hrelec; Sjekavica, Ivica; Pavlov, Katarina Horvat; Vidović, Tinka; Vlainić, Josipa; Stupnišek, Mirjana; Seiwerth, Sven; Sikirić, Predrag

doi:10.1016/j.vph.2018.02.010

Cited by 52 publications

(767 citation statements)

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“…A recently published review by Seiwerth et al (2018) used the current understanding from tendon, ligament and bone and applied this to gastrointestinal tract healing, which could provide a pathway for understanding of the systemic healing capabilities for applications to other tissues. Contemporary studies looking at animal models with diseases that affect the vascular and endothelial systems have also provided new insight into how BPC 157 works (Radeljak et al 2004;Sever et al 2009;Duzel et al 2017;Sikiric et al 2018;Vukojević et al 2018).…”

Section: Limitations Of Current Studiesmentioning

confidence: 99%

“…Furthermore, BPC 157 inhibits the growth of several tumour lines and can counteract tumour cachexia (Kang et al 2018). Vukojević et al (2018) and Duzel et al (2017) recently submitted works utilising BPC 157 for the treatment of inferior caval vein ligatures and colitis in rats, respectively. ICV is used to represent Virchow's triad-hypercoagulability, heamodynamic changes and endothelial injury/dysfunctionand represents a subset of deep vein thrombosis (DVT).…”

Section: Limitations Of Current Studiesmentioning

confidence: 99%

“…ICV is used to represent Virchow's triad-hypercoagulability, heamodynamic changes and endothelial injury/dysfunctionand represents a subset of deep vein thrombosis (DVT). Application of BPC 157, which has innate endotheium protective properties, counteracted direct vein injuries, thrombosis and thrombocytopenia and prolonged bleeding (Vukojević et al 2018). Furthermore, additional detrimenal consequences of ICV ligation were completely eliminated.…”

Section: Limitations Of Current Studiesmentioning

confidence: 99%

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Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

2019

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There is a current need for a therapy that can alleviate the social and economic burden that presents itself with debilitating and recurring musculoskeletal soft tissue injuries and disorders. Currently, several therapies are emerging and undergoing trials in animal models; these focus on the manipulation and administration of several growth factors implicated with healing. However, limitations include in vivo instability, reliance on biocompatible and robust carriers and restricted application procedures (local and direct). The aim of this paper is therefore to critically review the current literature surrounding the use of BPC 157, as a feasible therapy for healing and functional restoration of soft tissue damage, with a focus on tendon, ligament and skeletal muscle healing. Currently, all studies investigating BPC 157 have demonstrated consistently positive and prompt healing effects for various injury types, both traumatic and systemic and for a plethora of soft tissues. However, to date, the majority of studies have been performed on small rodent models and the efficacy of BPC 157 is yet to be confirmed in humans. Further, over the past two decades, only a handful of research groups have performed in-depth studies regarding this peptide. Despite this, it is apparent that BPC 157 has huge potential and following further development has promise as a therapy to conservatively treat or aid recovery in hypovascular and hypocellular soft tissues such as tendon and ligaments. Moreover, skeletal muscle injury models have suggested a beneficial effect not only for disturbances that occur as a result of direct trauma but also for systemic insults including hyperkalamia and hypermagnesia. Promisingly, there are few studies reporting any adverse reactions to the administration of BPC 157, although there is still a need to understand the precise healing mechanisms for this therapy to achieve clinical realisation.

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Section: Limitations Of Current Studiesmentioning

confidence: 99%

Section: Limitations Of Current Studiesmentioning

confidence: 99%

Section: Limitations Of Current Studiesmentioning

confidence: 99%

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Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

2019

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“…The abnormal processing of sensory inputs in the CNS [68]. Moreover, evidence that the compromised white matter integrity of specific spinal pathways has been linked to clinical disability [69][70][71], and cortical reorganization [72] should be considered in relation to the pleiotropic beneficial effect of BPC 157 administration observed in distinctive brain areas and lesions [32][33][34][35][36][37][38][39][40]. These beneficial effects include the counteractions of traumatic brain injury and severe encephalopathies after NSAID overdose, insulin overdose, magnesium overdose, and exposure to the neurotoxin cuprizone in a rat model of multiple sclerosis [33][34][35][36][37][38][39][40][41].…”

Section: Discussionmentioning

confidence: 99%

“…In comparison, the stable gastric pentadecapeptide BPC 157, an emerging treatment with potential therapeutic applications, appears to be unrestricted by the limitations seen in previous therapies. The stable gastric pentadecapeptide BPC 157, an original cytoprotective antiulcer peptide that is used in ulcerative colitis and recently in a multiple sclerosis trial and that has an LD1 that has not been achieved [1][2][3][4][5][6][7][8][9][10][11], is known to have pleiotropic beneficial effects [1][2][3][4][5][6][7][8][9][10][11] and to interact with several molecular pathways [2,[27][28][29][30][31][32]. BPC 157 has beneficial effects on inflammation, hemorrhage, and edema after traumatic brain injury [33], various severe encephalopathies (which follow gastrointestinal and/or liver lesions), NSAID overdose [34][35][36][37], or insulin overdose seizures [38] and on severe muscle weakness after exposure to the specific neurotoxin cuprizone in a rat multiple sclerosis model [39] or magnesium overdose [40].…”

Section: Introductionmentioning

confidence: 99%

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

et al. 2019

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Background: We focused on the therapeutic effects of the stable gastric pentadecapeptide BPC 157 in spinal cord injury using a rat model. BPC 157, of which the LD1 has not been achieved, has been implemented as an anti-ulcer peptide in inflammatory bowel disease trials and recently in a multiple sclerosis trial. In animals, BPC 157 has an anti-inflammatory effect and therapeutic effects in functional recovery and the rescue of somatosensory neurons in the sciatic nerve after transection, upon brain injury after concussive trauma, and in severe encephalopathies. Additionally, BPC 157 affects various molecular pathways. Methods: Therefore, BPC 157 therapy was administered by a one-time intraperitoneal injection (BPC 157 (200 or 2 μg/kg) or 0.9% NaCl (5 ml/kg)) 10 min after injury. The injury procedure involved laminectomy (level L2-L3) and a 60-s compression (neurosurgical piston (60-66 g) of the exposed dural sac of the sacrocaudal spinal cord). Assessments were performed at 1, 4, 7, 15, 30, 90, 180, and 360 days after injury. Results: All of the injured rats that received BPC 157 exhibited consistent clinical improvement, increasingly better motor function of the tail, no autotomy, and resolved spasticity by day 15. BPC 157 application largely counteracted changes at the microscopic level, including the formation of vacuoles and the loss of axons in the white matter, the formation of edema and the loss of motoneurons in the gray matter, and a decreased number of large myelinated axons in the rat caudal nerve from day 7. EMG recordings showed a markedly lower motor unit potential in the tail muscle. Conclusion: Axonal and neuronal necrosis, demyelination, and cyst formation were counteracted. The functional rescue provided by BPC 157 after spinal cord injury implies that BPC 157 therapy can impact all stages of the secondary injury phase.

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

et al. 2020

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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.

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Rat inferior caval vein (ICV) ligature and particular new insights with the stable gastric pentadecapeptide BPC 157

Cited by 52 publications

References 50 publications

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

Gastric pentadecapeptide body protection compound BPC 157 and its role in accelerating musculoskeletal soft tissue healing

Stable gastric pentadecapeptide BPC 157 can improve the healing course of spinal cord injury and lead to functional recovery in rats

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

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