Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine

Amić, Fedor and Drmić, Domagoj and Bilić, Zdenko and Krežić, Ivan and Žizek, Helena and Peklić, Marina and Kliček, Robert and Pajtak, Alen and Amić, Enio and Vidović, Tinka and Rakić, Mislav and Milković Periša, Marija and Horvat Pavlov, Katarina and Kokot, Antonio and Tvrdeić, Ante and Boban Blagaić, Alenka and Zovak, Mario and Seiwerth, Sven and Sikirić, Predrag (2018) Bypassing major venous occlusion and duodenal lesions in rats, and therapy with the stable gastric pentadecapeptide BPC 157, L-NAME and L-arginine. World Journal of Gastroenterology, 24 (47). pp. 5366-5378. ISSN 1007-9327

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Abstract

AIM: To investigate whether duodenal lesions induced by major venous occlusions can be attenuated by BPC 157 regardless nitric oxide (NO) system involvement. ----- METHODS: Male Wistar rats underwent superior anterior pancreaticoduodenal vein (SAPDV)-ligation and were treated with a bath at the ligated SAPDV site (BPC 157 10 μg, 10 ng/kg per 1 mL bath/rat; L-NAME 5 mg/kg per 1 mL bath/rat; L-arginine 100 mg/kg per 1 mL bath/rat, alone and/or together; or BPC 157 10 μg/kg instilled into the rat stomach, at 1 min ligation-time). We recorded the vessel presentation (filled/appearance or emptied/disappearance) between the 5 arcade vessels arising from the SAPDV on the ventral duodenum side, the inferior anterior pancreaticoduodenal vein (IAPDV) and superior mesenteric vein (SMV) as bypassing vascular pathway to document the duodenal lesions presentation; increased NO- and oxidative stress [malondialdehyde (MDA)]-levels in duodenum. ----- RESULTS: Unlike the severe course in the SAPDV-ligated controls, after BPC 157 application, the rats exhibited strong attenuation of the mucosal lesions and serosal congestion, improved vessel presentation, increased interconnections, increased branching by more than 60% from the initial value, the IAPDV and SMV were not congested. Interestingly, after 5 min and 30 min of L-NAME and L-arginine treatment alone, decreased mucosal and serosal duodenal lesions were observed; their effect was worsened at 24 h, and no effect on the collateral vessels and branching was seen. Together, L-NAME+L-arginine antagonized each other's response, and thus, there was an NO-related effect. With BPC 157, all SAPDV-ligated rats receiving L-NAME and/or L-arginine appeared similar to the rats treated with BPC 157 alone. Also, BPC 157 in SAPDV-ligated rats normalized levels of NO and MDA, two oxidative stress markers, in duodenal tissues. ----- CONCLUSION: BPC 157, rapidly bypassing occlusion, rescued the original duodenal flow through IAPDV to SMV flow, an effect related to the NO system and reduction of free radical formation.

Item Type: Article
Additional Information: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/ licenses/by-nc/4.0/
MeSH: Animals ; Arginine/pharmacology ; Arginine/therapeutic use ; Colitis, Ischemic/drug therapy ; Colitis, Ischemic/etiology ; Collateral Circulation/drug effects ; Disease Models, Animal ; Duodenum/blood supply ; Duodenum/drug effects ; Duodenum/pathology ; Humans ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; NG-Nitroarginine Methyl Ester/therapeutic use ; Nitric Oxide/metabolism ; Oxidative Stress/drug effects ; Peptide Fragments/pharmacology ; Peptide Fragments/therapeutic use ; Protective Agents/pharmacology ; Protective Agents/therapeutic use ; Proteins/pharmacology ; Proteins/therapeutic use ; Random Allocation ; Rats ; Rats, Wistar ; Treatment Outcome ; Veins/drug effects ; Venous Thrombosis/complications
Departments: Katedra za farmakologiju
Katedra za patologiju
Depositing User: Anja Majstorović
Status: Published
Creators:
CreatorsEmail
Amić, FedorUNSPECIFIED
Drmić, DomagojUNSPECIFIED
Bilić, ZdenkoUNSPECIFIED
Krežić, IvanUNSPECIFIED
Žizek, HelenaUNSPECIFIED
Peklić, MarinaUNSPECIFIED
Kliček, RobertUNSPECIFIED
Pajtak, AlenUNSPECIFIED
Amić, EnioUNSPECIFIED
Vidović, TinkaUNSPECIFIED
Rakić, MislavUNSPECIFIED
Milković Periša, MarijaUNSPECIFIED
Horvat Pavlov, KatarinaUNSPECIFIED
Kokot, AntonioUNSPECIFIED
Tvrdeić, AnteUNSPECIFIED
Boban Blagaić, AlenkaUNSPECIFIED
Zovak, MarioUNSPECIFIED
Seiwerth, SvenUNSPECIFIED
Sikirić, PredragUNSPECIFIED
Date: 21 December 2018
Date Deposited: 19 Jun 2019 10:57
Last Modified: 19 Jun 2019 11:00
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/3288

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