Robert’s Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157
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,
Predrag Sikiric
Affiliations
Slaven Gojkovic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Ivan Krezic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Hrvoje Vranes
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Helena Zizek
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Domagoj Drmic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Lovorka Batelja Vuletic
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Marija Milavic
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Suncana Sikiric
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Irma Stilinovic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Paris Simeon
Department of Endodontics and Restorative Dentistry, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia
Mario Knezevic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Toni Kolak
Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Marijan Tepes
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Karol Simonji
Internal Diseases Clinic, Faculty of Veterinary Medicine, University of Zagreb, 10000 Zagreb, Croatia
Sanja Strbe
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Nora Nikolac Gabaj
Department of Chemistry, University Clinical Hospital Center “Sestre Milosrdnice”, 10000 Zagreb, Croatia
Ivan Barisic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Emma Grace Oreskovic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Eva Lovric
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Antonio Kokot
Department of Anatomy and Neuroscience, School of Medicine, J.J. Strossmayer University of Osijek, 31000 Osijek, Croatia
Anita Skrtic
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Alenka Boban Blagaic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Sven Seiwerth
Department of Pathology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Predrag Sikiric
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
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.