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Gojkovic, Slaven; Krezic, Ivan; Vranes, Hrvoje; Zizek, Helena; Drmic, Domagoj; Batelja Vuletic, Lovorka; Milavic, Marija; Sikiric, Suncana; Stilinovic, Irma; Simeon, Paris; Knezevic, Mario; Kolak, Toni; Tepes, Marijan; Simonji, Karol; Strbe, Sanja; Nikolac Gabaj, Nora; Barisic, Ivan; Oreskovic, Emma Grace; Lovric, Eva; Kokot, Antonio; Skrtic, Anita; Boban Blagaic, Alenka; Seiwerth, Sven; Sikiric, Predrag
Biomedicines, 09/2021, Letnik: 9, Številka: 10Journal Article
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.
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