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 Gojković ,Toni Kolak,Antonio Kokot,Sven Seiwerth,Nora Nikolac Gabaj,Irma Stilinovic,Paris Simeon,Karol Šimonji ,Sanja Štrbe ,Helena Žižek ,Lovorka Batelja Vuletić ,Emma Orešković ,Sunčana Sikirić ,Ivan Barišić ,Ivan Krezić ,Anita Škrtić ,Hrvoje Vraneš ,Martina Knežević ,Domagoj Drmić ,Marijan Tepeš ,Alenka Boban Blagaić ,Marija Milavić ,Eva Lovrić ,Predrag Sikirić

doi:10.3390/biomedicines9101300

Slaven Gojković , Toni Kolak + Show 22 more

Open Access

https://doi.org/10.3390/biomedicines9101300

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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.

Highlights

This study attempts to clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish a prospective cytoprotective treatment.Cytoprotection is one of the most important concepts in gastroenterology and pharmacology [1,2,3]
A likely interpretation is that BPC 157 administration may have extended the innate cytoprotective effect, the vascular effect that is rapidly activated by intragastric alcohol exposure
The course was markedly counteracted with BPC 157 therapy

Summary

Introduction

This study attempts to clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish a prospective cytoprotective treatment.Cytoprotection is one of the most important concepts in gastroenterology and pharmacology [1,2,3]. We assumed that intragastric alcohol administration causes similar widespread dysfunction to that observed in rats after the occlusion of peripheral [11,12,13,14,15,16] and central [17] vessels These peripheral and central deficits include severe gastric lesions [4], intracranial (superior sagittal sinus) hypertension, brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, peripheral and central thrombosis, inferior and superior vena caval congestion, azygos vein failure, electrocardiogram (ECG) disturbances, and heart, lung, liver and kidney lesions. This syndrome could have prominent screening potential for the cytoprotective activity of anti-ulcer agents

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