Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion

Kolovrat, Marijan; Gojkovic, Slaven; Krezic, Ivan; Malekinusic, Dominik; Vrdoljak, Borna; Kovac, Katarina Kasnik; Kralj, Tamara; Drmic, Domagoj; Barišić, Ivan; Pavlov, Katarina Horvat; Petrović, Andreja; Duzel, Antonija; Knežević, Martina; Mirković, Ivan; Kokot, Antonio; Blagaić, Alenka Boban; Seiwerth, Sven; Sikirić, Predrag

doi:10.4254/wjh.v12.i5.184

Cited by 34 publications

(601 citation statements)

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“…Evidently, this initial L-NAME-induced defect and subsequent course prompted a particular chain of events. As mentioned above, this may be comparable to the complete occlusion (ligation)-induced defects produced in the other vessels and consequent syndromes (Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020). In particular experiments, the infrarenal inferior caval vein (Vukojevic et al, 2018), suprahepatic inferior caval vein (Gojkovic et al, 2020), superior anterior pancreaticoduodenal vein (Amic et al,FIGURE 5 | Retrobulbar L-NAME application-induced retinal damage as fundus assessment by fundoscopy.…”

Section: Discussionmentioning

confidence: 69%

“…2018), portal vein and hepatic artery (Kolovrat et al, 2020), and left colic artery and vein (Duzel et al, 2017) were occluded. Consequently, we noted portal and caval hypertension, aortal hypotension, ECG disturbances, arterial and venous thrombosis, and organ lesions (Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…To illustrate its modulatory role on NO-system functions ( Sikiric et al, 2014 ), BPC 157 may counteract L-NAME hypertension and pro-thrombotic effect as well as L-arginine hypotension and antithrombotic effect ( Sikiric et al, 1997 ; Stupnisek et al, 2015 ), and induce its own NO-release ( Sikiric et al, 1997 ; Turkovic et al, 2004 ). Also, BPC 157 may be the free radical scavenger to counteract reperfusion-induced free radical injury ( Belosic Halle et al, 2017 ; Duzel et al, 2017 ; Luetic et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Vukojevic et al, 2018 ; Sever et al, 2019 ; Sucic et al, 2019 ; Kolovrat et al, 2020 ; Park et al, 2020 ). In addition, BPC 157, as an agent with cytoprotective effect in the entire gastrointestinal tract (and thereby, innate endothelium protection) ( Sikiric et al, 2018 ; Sikiric et al, 2020 ), prevents and reverses thrombosis formation ( Hrelec et al, 2009 ; Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Also, BPC 157 may be the free radical scavenger to counteract reperfusion-induced free radical injury ( Belosic Halle et al, 2017 ; Duzel et al, 2017 ; Luetic et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Vukojevic et al, 2018 ; Sever et al, 2019 ; Sucic et al, 2019 ; Kolovrat et al, 2020 ; Park et al, 2020 ). In addition, BPC 157, as an agent with cytoprotective effect in the entire gastrointestinal tract (and thereby, innate endothelium protection) ( Sikiric et al, 2018 ; Sikiric et al, 2020 ), prevents and reverses thrombosis formation ( Hrelec et al, 2009 ; Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ). The evidence is provided after abdominal aorta anastomosis ( Hrelec et al, 2009 ) or major vein occlusion ( Vukojevic et al, 2018 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

et al. 2021

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Providing NO-system importance, we suggest that one single application of the NOS-blocker L-NAME may induce retinal ischemia in rats, and that the stable pentadecapeptide BPC 157 may be the therapy, since it may interact with the NO-system and may counteract various adverse effects of L-NAME application. A rat retinal ischemia study was conducted throughout 4 weeks, including fundoscopy, behavior presentation, tonometry, and histology assessment. Retrobulbar L-NAME application (5 mg/kg; 0.5 mg/0.1 ml saline/each eye) in rats immediately produced moderate generalized irregularity in the diameter of blood vessels with moderate atrophy of the optic disc and faint presentation of the choroidal blood vessels, and these lesions rapidly progressed to the severe stage. The specific L-NAME–induced vascular failure points to normal intraocular pressure (except to very transitory increase upon drug retrobulbar administration). When BPC 157 (10 μg; 10 ng/kg, as retrobulbar application, 1 μg; 1 ng/0.1 ml saline/each eye) is given at either 20 min after L-NAME or, lately, at 48 h after L-NAME, the regular retrobulbar L-NAME injection findings disappear. Instead, fundoscopy demonstrated only discrete generalized vessel caliber irregularity with mild atrophy of the optic disc, and then, quite rapidly, normal eye background and choroidal blood vessels, which remain in all of the subsequent periods. Also, histology assessment at 1, 2, and 4 weeks shows that BPC 157 counteracted the damaged inner plexiform layer and inner nuclear layer, and revealed normal retinal thickness. The poor behavioral presentation was also rescued. Thus, while further studies will be done, BPC 157 counteracted L-NAME–induced rat retinal ischemia.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

et al. 2021

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“… 12 , 13 Angiogenesis stimulates wound healing by forming new blood vessels from pre-existing vessels, within a few days, these are organized into a microvascular network throughout the granulation tissue. Numerous papers have reported that stable gastric pentadecapeptide BPC 157 can regulate angiogenesis during the healing process by rescuing the duodenal lesions in rats through interacting with the nitric oxide (NO) system and reducing of free radical formation, 14 and also can resolve pringle maneuver 15 and hippocampal ischemic damage in rats due to ischemia or reperfusion. 16 Its strong angiogenic effect is mainly via activation of the VEGF-AKT-eNOS signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

<p>Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157</p>

Wu¹,

Wei²,

Li³

et al. 2020

DDDT

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Aim Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury. Methods We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A ( VEGF-A ) and CD34 were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker CHOP , angiogenic markers VEGF-A and its receptor VEGFR1 , and endothelial NO synthase ( eNOS ) were all analyzed by Western blot. Results This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and eNOS . Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B ( AKT ) and p38 mitogen-activated protein kinase ( p38/MAPK ). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa. Conclusion In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via VEGF-A/VEGFR1 mediated- AKT/p38/MAPK signaling pathways.

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New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection

Sikiric,

Sever,

Krezic

et al. 2024

Inflammopharmacol

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Pentadecapeptide BPC 157 resolves Pringle maneuver in rats, both ischemia and reperfusion

Cited by 34 publications

References 56 publications

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

BPC 157 as a Therapy for Retinal Ischemia Induced by Retrobulbar Application of L-NAME in Rats

<p>Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157</p>

New studies with stable gastric pentadecapeptide protecting gastrointestinal tract. significance of counteraction of vascular and multiorgan failure of occlusion/occlusion-like syndrome in cytoprotection/organoprotection

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