Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats

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

doi:10.4291/wjgp.v11.i1.1

Cited by 32 publications

(551 citation statements)

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“…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. L-NAME retrobulbar application (total dose 5 mg/kg, which was divided by retrobulbar application in each eye, 0.5 mg/0.1 ml saline/eye).…”

Section: Discussionmentioning

confidence: 69%

“…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). Therefore, confronted with vessel occlusion (Duzel et al, 2017;Amic et al, 2018;Drmic et al, 2018;Vukojevic et al, 2018;Cesar et al, 2020;Gojkovic et al, 2020;Kolovrat et al, 2020), BPC 157 therapy effect was ascribed to the rapid opening of the collateral pathways to reestablish blood flow and compensate permanent occlusion of the vessel. Accordingly, the concomitant syndromes were fully counteracted (Vukojevic et al, 2018;Gojkovic et al, 2020;Kolovrat et al, 2020).…”

Section: Discussionmentioning

confidence: 97%

“…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%

“…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 ). Also, BPC 157 maintains thrombocytes function ( Konosic et al, 2019 ) without interfering with coagulation pathways ( Konosic et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Also, BPC 157 maintains thrombocytes function ( Konosic et al, 2019 ) without interfering with coagulation pathways ( Konosic et al, 2019 ). Finally, when confronted with major vessel occlusion, BPC 157 administration recruits vessels to rapidly activate the collateral pathway ( Duzel et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Vukojevic et al, 2018 ; Cesar et al, 2020 ; Gojkovic et al, 2020 ; Kolovrat et al, 2020 ). These responses effectively negate the harmful effect of L-NAME–NOS blockade ( Duzel et al, 2017 ; Amic et al, 2018 ; Drmic et al, 2018 ; Cesar 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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