Therapy Effect of the Stable Gastric Pentadecapeptide BPC 157 on Acute Pancreatitis as Vascular Failure-Induced Severe Peripheral and Central Syndrome in Rats
Ivan Maria Smoday,
Igor Petrovic,
Luka Kalogjera,
Hrvoje Vranes,
Helena Zizek,
Ivan Krezic,
Slaven Gojkovic,
Ivan Skorak,
Klaudija Hriberski,
Ivan Brizic,
Milovan Kubat,
Sanja Strbe,
Ivan Barisic,
Marija Sola,
Eva Lovric,
Marin Lozic,
Alenka Boban Blagaic,
Anita Skrtic,
Sven Seiwerth,
Predrag Sikiric
Affiliations
Ivan Maria Smoday
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Igor Petrovic
Department of Surgery, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Luka Kalogjera
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
Ivan Krezic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Slaven Gojkovic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Ivan Skorak
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Klaudija Hriberski
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Ivan Brizic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Milovan Kubat
Department of Forensic Medicine and Criminology, School of Medicne, 10000 Zagreb, Croatia
Sanja Strbe
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Ivan Barisic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Marija Sola
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
Marin Lozic
Department of Pediatric and Preventive Dentistry, School of Dental Medicine, University of Zagreb, 10000 Zagreb, Croatia
Alenka Boban Blagaic
Department of Pharmacology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Anita Skrtic
Department of Pathology, 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 revealed the therapy effect of the stable gastric pentadecapeptide BPC 157 (10 μg/kg, 10 ng/kg ig or po) with specific activation of the collateral rescuing pathways, the azygos vein, on bile duct ligation in particular, and acute pancreatitis as local disturbances (i.e., improved gross and microscopy presentation, decreased amylase level). Additionally, we revealed the therapy’s effect on the acute pancreatitis as vascular failure and multiorgan failure, both peripherally and centrally following “occlusion-like” syndrome, major intoxication (alcohol, lithium), maintained severe intra-abdominal hypertension, and myocardial infarction, or occlusion syndrome, and major vessel occlusion. The application-sacrifice periods were ligation times of 0–30 min, 0–5 h, 0–24 h (cured periods, early regimen) and 4.30 h–5 h, 5 h–24 h (cured periods, delayed regimen). Otherwise, bile duct-ligated rats commonly presented intracranial (superior sagittal sinus), portal and caval hypertension and aortal hypotension, gross brain swelling, hemorrhage and lesions, heart dysfunction, lung lesions, liver and kidney failure, gastrointestinal lesions, and severe arterial and venous thrombosis, peripherally and centrally. Unless antagonized with the key effect of BPC 157 regimens, reversal of the inferior caval and superior mesenteric vein congestion and reversal of the failed azygos vein activated azygos vein-recruited direct delivery to rescue the inferior-superior caval vein pathway; these were all antecedent to acute pancreatitis major lesions (i.e., acinar, fat necrosis, hemorrhage). These lesions appeared in the later period, but were markedly attenuated/eliminated (i.e., hemorrhage) in BPC 157-treated rats. To summarize, while the innate vicious cycle may be peripheral (bile duct ligation), or central (rapidly developed brain disturbances), or peripheral and central, BPC 157 resolved acute pancreatitis and its adjacent syndrome.