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Frontiers in Pentadecapeptide BPC 157

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 45260

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Prof. Dr. Predrag Sikiric

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Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Interests: gastrointestinal tract; CNS; cytoprotection; blood vessels; stable gastric pentadecapeptide BPC 157
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Prof. Dr. Sven Seiwerth

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Department of Pathology, School of Medicine, University of Zagreb, Šalata ul. 2, 10000, Zagreb, Croatia
Interests: wound healing; angiogenesis; tissue reaction to injury; carcinogenesis; metastasis
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Prof. Dr. Gábor Varga

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Department of Oral Biology, Semmelweis University, Nagyvárad Square 4, H-1089 Budapest, Hungary
Interests: GI epithelial function; molecular physiology; stem cell research and regenerative medicine of oral structures; tissue engineering applications
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Prof. Dr. Ki-Baik Hahm

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Digestive Disease Center, CHA Bundang Medical Center, CHA University School of Medicine, 120 Haeryong-ro, Seongnam, Korea
Interests: gastric cytoprotection; inflammation and resolution; cancer prevention
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This special issue deals with a native gastric peptide, resistant and stable in the human gastric juice, membrane stabilizer, counteracting gut-leaky syndrome, the stable gastric pentadecapeptide BPC 157, as a particular target, distinctive from the standard peptide growth factors, with particular molecular pathways involved, controlling VEGF- and NO-pathways. In the early 1990s, pentadecapeptide BPC 157 appeared as a late outbreak of the Robert’s and Szabo’s cytoprotection - organoprotection concept, and previous theoretical/practical breakthrough in the 1980s, and brain-gut axis and gut-brain axis, and as the time went on, with its reported effects, likely most useful confirmation of theory in practical implementation and justification. Against various noxious agents causing direct cell injury, the epithelial and endothelial integrity maintenance in the stomach (cytoprotection) and in the other tissues (organoprotection) was not fully realized with the standard cytoprotective agents (i.e., prostaglandins, before sulfhydrils, CRF, EGF, somatostatin, and dopamine agonists) acting through cytoprotective defensive system. As novel mediator, BPC 157 was coming after the evidenced point of their limited beneficial effects, and NO-system importance widely introduced, but vigorously established interconnection with these important systems (i.e., prostaglandins, dopamine, serotonin, NO). Thereby, BPC 157 therapy has pleiotropic beneficial effect. In addition to the beneficial effect on the entire gastrointestinal tract, and other organs various agents- and/or noxious procedures-induced lesions (liver (cirrhosis), lung, heart, spinal cord and brain), and considerable wound healing (i.e., skin, muscle, tendon, ligament, bone) (and especial wound, i.e., corneal ulcer), it may include counteraction of the depression-models, schizophrenia positive symptom-models and catalepsy-models. Recently, BPC 157 counteracts the vascular occlusion disturbances and blood pressure disturbances (relieving a Virchow's triad (endothelium lesions, hypercoagulability, stasis) situation) by rapid activation of the collateral vessel pathways.

You may choose our Joint Special Issue in Current Issues in Molecular Biology, or Joint Special Issue in International Journal of Molecular Sciences.

Prof. Dr. Predrag Sikiric
Prof. Dr. Sven Seiwerth
Prof. Dr. Gábor Varga
Prof. Dr. Ki-Baik Hahm
Guest Editors

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Keywords

Cytoprotection
Gastric pentadecapeptide BPC 157
Peptides, Healing
Tissues lesions
Blood vessels lesions
Wounds
Brain-gut axis
Inflammation and resolution
Cancer prevention
Therapy

Published Papers (11 papers)

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38 pages, 13926 KiB

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 May Counteract Myocardial Infarction Induced by Isoprenaline in Rats

by Ivan Barisic, Diana Balenovic, Mario Udovicic, Darija Bardak, Dean Strinic, Josipa Vlainić, Hrvoje Vranes, Ivan Maria Smoday, Ivan Krezic, Marija Milavic, Suncana Sikiric, Sandra Uzun, Gordana Zivanovic Posilovic, Sanja Strbe, Ivan Vukoja, Eva Lovric, Marin Lozic, Marko Sever, Martina Lovric Bencic, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric Show full author list Hide full author list

Biomedicines 2022, 10(2), 265; https://doi.org/10.3390/biomedicines10020265 - 26 Jan 2022

Cited by 16 | Viewed by 4352

Abstract

We revealed that the stable gastric pentadecapeptide BPC 157, a useful peptide therapy against isoprenaline myocardial infarction, as well as against isoprenaline myocardial reinfarction, may follow the counteraction of the recently described occlusion-like syndrome, induced peripherally and centrally, which was described for the first time in isoprenaline-treated rats. BPC 157 (10 ng/kg, 10 µg/kg i.p.), L-NAME (5 mg/kg i.p.), and L-arginine (200 mg/kg i.p.) were given alone or together at (i) 30 min before or, alternatively, (ii) at 5 min after isoprenaline (75 or 150 mg/kg s.c.). At 30 min after isoprenaline 75 mg/kg s.c., we noted an early multiorgan failure (brain, heart, lung, liver, kidney and gastrointestinal lesions), thrombosis, intracranial (superior sagittal sinus) hypertension, portal and caval hypertension, and aortal hypotension, in its full presentation (or attenuated by BPC 157 therapy (given at 5 min after isoprenaline) via activation of the azygos vein). Further, we studied isoprenaline (75 or 150 mg/kg s.c.) myocardial infarction (1 challenge) and reinfarction (isoprenaline at 0 h and 24 h, 2 challenges) in rats (assessed at the end of the subsequent 24 h period). BPC 157 reduced levels of all necrosis markers, CK, CK-MB, LDH, and cTnT, and attenuated gross (no visible infarcted area) and histological damage, ECG (no ST-T ischemic changes), and echocardiography (preservation of systolic left ventricular function) damage induced by isoprenaline. Its effect was associated with a significant decrease in oxidative stress parameters and likely maintained NO system function, providing that BPC 157 interacted with eNOS and COX2 gene expression in a particular way and counteracted the noxious effect of the NOS-blocker, L-NAME. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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26 pages, 7631 KiB

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 Therapy of Rat Glaucoma

by Tamara Kralj, Antonio Kokot, Mirna Zlatar, Sanja Masnec, Katarina Kasnik Kovac, Marija Milkovic Perisa, Lovorka Batelja Vuletic, Ana Giljanovic, Sanja Strbe, Suncana Sikiric, Slaven Balog, Bojan Sontacchi, Dijana Sontacchi, Matko Buljan, Eva Lovric, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric

Biomedicines 2022, 10(1), 89; https://doi.org/10.3390/biomedicines10010089 - 31 Dec 2021

Cited by 17 | Viewed by 2506

Abstract

Cauterization of three episcleral veins (open-angle glaucoma model) induces venous congestion and increases intraocular pressure in rats. If not upgraded, one episcleral vein is regularly unable to acquire and take over the whole function, and glaucoma-like features persist. Recently, the rapid upgrading of the collateral pathways by a stable gastric pentadecapeptide BPC 157 has cured many severe syndromes induced by permanent occlusion of major vessels, veins and/or arteries, peripherally and centrally. In a six-week study, medication was given prophylactically (immediately before glaucoma surgery, i.e., three episcleral veins cauterization) or as curative treatment (starting at 24 h after glaucoma surgery). The daily regimen of BPC 157 (0.4 µg/eye, 0.4 ng/eye; 10 µg/kg, 10 ng/kg) was administered locally as drops in each eye, intraperitoneally (last application at 24 h before sacrifice) or per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat until the sacrifice, first application being intragastric). Consequently, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, normal retinal and choroidal blood vessel presentation and normal optic nerve presentation. As leading symptoms, increased intraocular pressure and mydriasis, as well as degeneration of retinal ganglion cells, optic nerve head excavation and reduction in optic nerve thickness, generalized severe irregularity of retinal vessels, faint presentation of choroidal vessels and severe optic nerve disc atrophy were all counteracted. In conclusion, we claim that the reversal of the episcleral veins cauterization glaucoma appeared as a consequence of the BPC 157 therapy of the vessel occlusion-induced perilous syndrome. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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30 pages, 17212 KiB

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats

by Mladen Japjec, Katarina Horvat Pavlov, Andreja Petrovic, Mario Staresinic, Bozidar Sebecic, Matko Buljan, Hrvoje Vranes, Ana Giljanovic, Domagoj Drmic, Miroslav Japjec, Andreja Prtoric, Eva Lovric, Lovorka Batelja Vuletic, Ivan Dobric, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Sikiric Predrag

Biomedicines 2021, 9(11), 1547; https://doi.org/10.3390/biomedicines9111547 - 27 Oct 2021

Cited by 10 | Viewed by 4085

Abstract

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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40 pages, 18917 KiB

Open AccessArticle

Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157

by Sanja Strbe, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Hrvoje Vranes, Ivan Barisic, Dean Strinic, Tatjana Orct, Jaksa Vukojevic, Spomenko Ilic, Eva Lovric, Darija Muzinic, Danijela Kolenc, Igor Filipčić, Zoran Zoricic, Darko Marcinko, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric

Biomedicines 2021, 9(11), 1506; https://doi.org/10.3390/biomedicines9111506 - 20 Oct 2021

Cited by 21 | Viewed by 2956

Abstract

Due to endothelial impairment, high-dose lithium may produce an occlusive-like syndrome, comparable to permanent occlusion of major vessel-induced syndromes in rats; intracranial, portal, and caval hypertension, and aortal hypotension; multi-organ dysfunction syndrome; brain, heart, lung, liver, kidney, and gastrointestinal lesions; arterial and venous thrombosis; and tissue oxidative stress. Stable gastric pentadecapeptide BPC 157 may be a means of therapy via activating loops (bypassing vessel occlusion) and counteracting major occlusion syndromes. Recently, BPC 157 counteracted the lithium sulfate regimen in rats (500 mg/kg/day, ip, for 3 days, with assessment at 210 min after each administration of lithium) and its severe syndrome (muscular weakness and prostration, reduced muscle fibers, myocardial infarction, and edema of various brain areas). Subsequently, BPC 157 also counteracted the lithium-induced occlusive-like syndrome; rapidly counteracted brain swelling and intracranial (superior sagittal sinus) hypertension, portal hypertension, and aortal hypotension, which otherwise would persist; counteracted vessel failure; abrogated congestion of the inferior caval and superior mesenteric veins; reversed azygos vein failure; and mitigated thrombosis (superior mesenteric vein and artery), congestion of the stomach, and major hemorrhagic lesions. Both regimens of BPC 157 administration also counteracted the previously described muscular weakness and prostration (as shown in microscopic and ECG recordings), myocardial congestion and infarction, in addition to edema and lesions in various brain areas; marked dilatation and central venous congestion in the liver; large areas of congestion and hemorrhage in the lung; and degeneration of proximal and distal tubules with cytoplasmic vacuolization in the kidney, attenuating oxidative stress. Thus, BPC 157 therapy overwhelmed high-dose lithium intoxication in rats. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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31 pages, 6061 KiB

Open AccessEditor’s ChoiceArticle

Robert’s Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157

by Slaven Gojkovic, Ivan Krezic, Hrvoje Vranes, Helena Zizek, Domagoj Drmic, Lovorka Batelja Vuletic, Marija Milavic, Suncana Sikiric, Irma Stilinovic, Paris Simeon, Mario Knezevic, Toni Kolak, Marijan Tepes, Karol Simonji, Sanja Strbe, Nora Nikolac Gabaj, Ivan Barisic, Emma Grace Oreskovic, Eva Lovric, Antonio Kokot, Anita Skrtic, Alenka Boban Blagaic, Sven Seiwerth and Predrag Sikiric Show full author list Hide full author list

Biomedicines 2021, 9(10), 1300; https://doi.org/10.3390/biomedicines9101300 - 23 Sep 2021

Cited by 21 | Viewed by 3441

Abstract

We redefined Robert’s prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert’s model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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19 pages, 8255 KiB

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 Heals Established Vesicovaginal Fistula and Counteracts Stone Formation in Rats

by Domagoj Rasic, Anita Zenko Sever, Fran Rasic, Sanja Strbe, Zarko Rasic, Antonija Djuzel, Bozidar Duplancic, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth, Predrag Sikiric and Marko Sever

Biomedicines 2021, 9(9), 1206; https://doi.org/10.3390/biomedicines9091206 - 13 Sep 2021

Cited by 7 | Viewed by 3054

Abstract

With the stable gastric pentadecapeptide BPC 157 therapy known to heal various both external and internal rat fistulas, we attempt to approach vesicovaginal fistula, continuous urine leaking through vagina, bladder stones, and a possible therapy solution among rats with well-formed 2 week-fistulas (vaginal/vesical 4 mm large defects) started with delayed therapy. Subsequent control fistula course (the subsequent 1, 2, 4, and 6 weeks) since beginning revealed the failed healing, fistula leaking, adhesions, urinary leaking through vagina, failed epithelization, collagenization, granulation tissue and neovascularization, increased inflammation, and necrosis. Thereby, the later intervals revealed the persistent inability to sustain even minimal volume, vesical, and vaginal defects and stone formation at the end of the experiment (fistula-time day 56). BPC 157 therapy (10 µg/kg, 10 ng/kg, intraperitoneally once time daily or perorally in drinking water until sacrifice) was initiated with a considerable delay (at 2 weeks after fistula formation). Already within 1 week therapy, all BPC 157 regimens stopped urinary leaking through vagina, reversed the otherwise resistant poor healing course to the increased epithelization, collagenization, granulation tissue and neovascularization, decreased inflammation, and decreased necrosis. Thereby, at later intervals, all BPC 157 rats exhibited a five times larger volume that can be sustained before leaking as in healthy, vesical, and vaginal defects completely closed and no stone formation. Thus, macro/microscopic and functional recovery, and counteracted stone formation. Concluding, BPC 157 therapy’s beneficial effects resulted in healing and no stone formation, with µg- and ng-regimens, either given daily perorally in drinking water or intraperitoneally. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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27 pages, 65502 KiB

Open AccessArticle

Complex Syndrome of the Complete Occlusion of the End of the Superior Mesenteric Vein, Opposed with the Stable Gastric Pentadecapeptide BPC 157 in Rats

by Mario Knezevic, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Hrvoje Vranes, Dominik Malekinusic, Borna Vrdoljak, Tamara Knezevic, Katarina Horvat Pavlov, Domagoj Drmic, Miro Staroveski, Antonija Djuzel, Zoran Rajkovic, Toni Kolak, Eva Lovric, Marija Milavic, Suncana Sikiric, Ivan Barisic, Marijan Tepes, Ante Tvrdeic, Leonardo Patrlj, Sanja Strbe, Marija Sola, Andrej Situm, Antonio Kokot, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric Show full author list Hide full author list

Biomedicines 2021, 9(8), 1029; https://doi.org/10.3390/biomedicines9081029 - 17 Aug 2021

Cited by 23 | Viewed by 2470

Abstract

Background. Gastric pentadecapeptide BPC 157 therapy in rats compensated irremovable occlusion of various vessels and counteracted the consequent multiorgan dysfunction syndromes by activation of the corresponding collateral bypassing loops. Thus, we used BPC 157 therapy against the irremovable occlusion of the end of the superior mesenteric vein. Methods. Assessments, for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress) include the portal and caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension, systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, and heart, lung, liver, kidney and gastrointestinal tract, in particular, and brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus) lesions. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 or 15 min ligation time. Results. BPC 157 rapidly activated the superior mesenteric vein–inferior anterior pancreati-coduodenal vein–superior anterior pancreaticoduodenal vein–pyloric vein–portal vein pathway, reestablished superior mesenteric vein and portal vein connection and reestablished blood flow. Simultaneously, toward inferior caval vein, an additional pathway appears via the inferior mesenteric vein united with the middle colic vein, throughout its left colic branch to ascertain alternative bypassing blood flow. Consequently, BPC 157 acts peripherally and centrally, and counteracted the intracranial (superior sagittal sinus), portal and caval hypertension, aortal hypotension, ECG disturbances attenuated, abolished progressing venous and arterial thrombosis. Additionally, BPC 157 counteracted multiorgan dysfunction syndrome, heart, lung, liver, kidney and gastrointestinal tract, and brain lesions, and oxidative stress in tissues. Conclusion. BPC 157 therapy may be specific management also for the superior mesenteric vein injuries. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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17 pages, 3701 KiB

Open AccessArticle

Stable Gastric Pentadecapeptide BPC 157 Therapy for Monocrotaline-Induced Pulmonary Hypertension in Rats Leads to Prevention and Reversal

by Mario Udovicic, Marko Sever, Lovro Kavur, Kristina Loncaric, Ivan Barisic, Diana Balenovic, Gordana Zivanovic Posilovic, Dean Strinic, Sandra Uzun, Lovorka Batelja Vuletic, Suncana Sikiric, Anita Skrtic, Domagoj Drmic, Alenka Boban Blagaic, Martina Lovric Bencic, Sven Seiwerth and Predrag Sikiric

Biomedicines 2021, 9(7), 822; https://doi.org/10.3390/biomedicines9070822 - 15 Jul 2021

Cited by 14 | Viewed by 4535

Abstract

Background. Monocrotaline selectively injures the lung’s vascular endothelium and induces pulmonary arterial hypertension. The stable gastric pentadecapeptide BPC 157 acts as a prototype cytoprotective agent that maintains endothelium, and its application may be a novel therapy. Besides, BPC 157 prevents and reverses thrombosis formation, maintains platelet function, alleviates peripheral vascular occlusion disturbances, and has anti-arrhythmic and anti-inflammatory effects. Monocrotaline-induced pulmonary arterial hypertension in rats (wall thickness, total vessel area, heart frequency, QRS axis deviation, QT interval prolongation, increase in right ventricle systolic pressure and bodyweight loss) can be counteracted with early or delayed BPC 157 therapy. Methods and Results. After monocrotaline (80 mg/kg subcutaneously), BPC 157 (10 μg/kg or 10 ng/kg, days 1–14 or days 1–30 (early regimens), or days 14–30 (delayed regimen)) was given once daily intraperitoneally (last application 24 h before sacrifice) or continuously in drinking water until sacrifice (day 14 or 30). Without therapy, the outcome was the full monocrotaline syndrome, marked by right-side heart hypertrophy and massive thickening of the precapillary artery’s smooth muscle layer, clinical deterioration, and sometimes death due to pulmonary hypertension and right-heart failure during the 4th week after monocrotaline injection. With all BPC 157 regimens, monocrotaline-induced pulmonary arterial hypertension (including all disturbed parameters) was counteracted, and consistent beneficial effects were documented during the whole course of the disease. Pulmonary hypertension was not even developed (early regimens) as quickly as the advanced pulmonary hypertension was rapidly attenuated and then completely eliminated (delayed regimen). Conclusions. Thus, pentadecapeptide BPC 157 prevents and counteracts monocrotaline-induced pulmonary arterial hypertension and cor pulmonale in rats. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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26 pages, 83622 KiB

Open AccessArticle

Occluded Superior Mesenteric Artery and Vein. Therapy with the Stable Gastric Pentadecapeptide BPC 157

by Mario Knezevic, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Dominik Malekinusic, Borna Vrdoljak, Tamara Knezevic, Hrvoje Vranes, Domagoj Drmic, Miro Staroveski, Antonija Djuzel, Zoran Rajkovic, Toni Kolak, Eva Lovric, Marija Milavic, Suncana Sikiric, Ante Tvrdeic, Leonardo Patrlj, Sanja Strbe, Marija Sola, Andrej Situm, Antonio Kokot, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric Show full author list Hide full author list

Biomedicines 2021, 9(7), 792; https://doi.org/10.3390/biomedicines9070792 - 8 Jul 2021

Cited by 24 | Viewed by 2737

Abstract

Background. We investigated the occluded essential vessel tributaries, both arterial and venous, occluded superior mesenteric vein and artery in rats, consequent noxious syndrome, peripherally and centrally. As therapy, we hypothesized the rapidly activated alternative bypassing pathways, arterial and venous, and the stable gastric pentadecapeptide BPC 157 since it rapidly alleviated venous occlusion syndromes. Methods. Assessments were performed for 30 min (gross recording, venography, ECG, pressure, microscopy, biochemistry, and oxidative stress), including portal hypertension, caval hypertension, aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis, ECG disturbances, MDA-tissue increase, the multiple organs lesions, heart, lung, liver, kidney and gastrointestinal tract, including brain (swelling, and cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus lesions). Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally at 1 min ligation-time. Results. BPC 157 rapidly activated collateral pathways. These collateral loops were the superior mesenteric vein-inferior anterior pancreaticoduodenal vein-superior anterior pancreaticoduodenal vein-pyloric vein-portal vein pathway, an alternative pathway toward inferior caval vein via the united middle colic vein and inferior mesenteric vein through the left colic vein, and the inferior anterior pancreaticoduodenal artery and inferior mesenteric artery. Consequently, BPC 157 counteracted the superior sagittal sinus, portal and caval hypertension, aortal hypotension, progressing venous and arterial thrombosis peripherally and centrally, ECG disturbances attenuated. Markedly, the multiple organs lesions, heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain lesions, and oxidative stress in tissues were attenuated. Conclusions. BPC 157 therapy rapidly recovered rats, which have complete occlusion of the superior mesenteric vein and artery. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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33 pages, 29125 KiB

Open AccessEditor’s ChoiceArticle

BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment

by Slaven Gojkovic, Ivan Krezic, Hrvoje Vranes, Helena Zizek, Domagoj Drmic, Katarina Horvat Pavlov, Andrea Petrovic, Lovorka Batelja Vuletic, Marija Milavic, Suncana Sikiric, Irma Stilinovic, Mariam Samara, Mario Knezevic, Ivan Barisic, Ivica Sjekavica, Eva Lovric, Anita Skrtic, Sven Seiwerth and Predrag Sikiric

Biomedicines 2021, 9(7), 744; https://doi.org/10.3390/biomedicines9070744 - 28 Jun 2021

Cited by 26 | Viewed by 7245

Abstract

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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29 pages, 10428 KiB

Open AccessEditor’s ChoiceArticle

Occlusion of the Superior Mesenteric Artery in Rats Reversed by Collateral Pathways Activation: Gastric Pentadecapeptide BPC 157 Therapy Counteracts Multiple Organ Dysfunction Syndrome; Intracranial, Portal, and Caval Hypertension; and Aortal Hypotension

by Mario Knezevic, Slaven Gojkovic, Ivan Krezic, Helena Zizek, Dominik Malekinusic, Borna Vrdoljak, Hrvoje Vranes, Tamara Knezevic, Ivan Barisic, Katarina Horvat Pavlov, Domagoj Drmic, Miro Staroveski, Antonija Djuzel, Zoran Rajkovic, Toni Kolak, Ivica Kocman, Eva Lovric, Marija Milavic, Suncana Sikiric, Ante Tvrdeic, Leonardo Patrlj, Sanja Strbe, Antonio Kokot, Alenka Boban Blagaic, Anita Skrtic, Sven Seiwerth and Predrag Sikiric Show full author list Hide full author list

Biomedicines 2021, 9(6), 609; https://doi.org/10.3390/biomedicines9060609 - 26 May 2021

Cited by 23 | Viewed by 3995

Abstract

Gastric pentadecapeptide BPC 157 therapy counteracts multiple organ dysfunction syndrome in rats, which have permanent occlusion of the superior mesenteric artery close to the abdominal aorta. Previously, when confronted with major vessel occlusion, its effect would rapidly activate collateral vessel pathways and resolve major venous occlusion syndromes (Pringle maneuver ischemia, reperfusion, Budd–Chiari syndrome) in rats. This would overwhelm superior mesenteric artery permanent occlusion, and result in local, peripheral, and central disturbances. Methods: Assessments, for 30 min (gross recording, angiography, ECG, pressure, microscopy, biochemistry, and oxidative stress), included the portal hypertension, caval hypertension, and aortal hypotension, and centrally, the superior sagittal sinus hypertension; systemic arterial and venous thrombosis; ECG disturbances; MDA-tissue increase; and multiple organ lesions and disturbances, including the heart, lung, liver, kidney, and gastrointestinal tract, in particular, as well as brain (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus). BPC 157 therapy (/kg, abdominal bath) (10 µg, 10 ng) was given for a 1-min ligation time. Results: BPC 157 rapidly recruits collateral vessels (inferior anterior pancreaticoduodenal artery and inferior mesenteric artery) that circumvent occlusion and ascertains blood flow distant from the occlusion in the superior mesenteric artery. Portal and caval hypertension, aortal hypotension, and, centrally, superior sagittal sinus hypertension were attenuated or eliminated, and ECG disturbances markedly mitigated. BPC 157 therapy almost annihilated venous and arterial thrombosis. Multiple organ lesions and disturbances (i.e., heart, lung, liver, and gastrointestinal tract, in particular, as well as brain) were largely attenuated. Conclusions: Rats with superior mesenteric artery occlusion may additionally undergo BPC 157 therapy as full counteraction of vascular occlusion-induced multiple organ dysfunction syndrome. Full article

(This article belongs to the Special Issue Frontiers in Pentadecapeptide BPC 157)

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