Esophagogastric anastomosis in rats: improved healing by BPC 157 and L-arginine, aggravated by L-NAME

Djaković, Željko and Djaković, Ivka and Cesarec, Vedran and Madžarac, Goran and Bečejac, Tomislav and Zukanović, Goran and Drmić, Domagoj and Batelja, Lovorka and Zenko Sever, Anita and Kolenc, Danijela and Pajtak, Alen and Knez, Nikica and Japjec, Mladen and Luetić, Krešimir and Stančić-Rokotov, Dinko and Seiwerth, Sven and Sikirić, Predrag (2016) Esophagogastric anastomosis in rats: improved healing by BPC 157 and L-arginine, aggravated by L-NAME. World Journal of Gastroenterology, 22 (41). pp. 9127-9140. ISSN 1007-9327

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AIM: To cure typically life-threatening esophagogastric anastomosis in rats, lacking anastomosis healing and sphincter function rescue, in particular. ----- METHODS: Because we assume esophagogastric fistulas represent a particular NO-system disability, we attempt to identify the benefits of anti-ulcer stable gastric pentadecapeptide BPC 157, which was in trials for ulcerative colitis and currently for multiple sclerosis, in rats with esophagocutaneous fistulas. Previously, BPC 157 therapies have promoted the healing of intestinal anastomosis and fistulas, and esophagitis and gastric lesions, along with rescued sphincter function. Additionally, BPC 157 particularly interacts with the NO-system. In the 4 d after esophagogastric anastomosis creation, rats received medication (/kg intraperitoneally once daily: BPC 157 (10 μg, 10 ng), L-NAME (5 mg), or L-arginine (100 mg) alone and/or combined or BPC 157 (10 μg, 10 ng) in drinking water). For rats underwent esophagogastric anastomosis, daily assessment included progressive stomach damage (sum of the longest diameters, mm), esophagitis (scored 0-5), weak anastomosis (mL H2O before leak), low pressure in esophagus at anastomosis and in the pyloric sphincter (cm H2O), progressive weight loss (g) and mortality. Immediate effect assessed blood vessels disappearance (scored 0-5) at the stomach surface immediately after anastomosis creation. ----- RESULTS: BPC 157 (all regimens) fully counteracted the perilous disease course from the very beginning (i.e., with the BPC 157 bath, blood vessels remained present at the gastric surface after anastomosis creation) and eliminated mortality. Additionally, BPC 157 treatment in combination with L-NAME nullified any effect of L-NAME that otherwise intensified the regular course. Consistently, with worsening (with L-NAME administration) and amelioration (with L-arginine), either L-arginine amelioration prevails (attenuated esophageal and gastric lesions) or they counteract each other (L-NAME + L-arginine); with the addition of BPC 157 (L-NAME + L-arginine + BPC 157), there was a marked beneficial effect. BPC 157 treatment for esophagogastric anastomosis, along with NOS-blocker L-NAME and/or NOS substrate L-arginine, demonstrated an innate NO-system disability (as observed with L-arginine effectiveness). BPC 157 distinctively affected corresponding events: worsening (obtained with L-NAME administration that was counteracted); or amelioration (L-arginine + BPC 157-rats correspond to BPC 157-rats). ----- CONCLUSION: Innate NO-system disability for esophagogastric anastomoses, including L-NAME-worsening, suggests that these effects could be corrected by L-arginine and almost completely eliminated by BPC 157 therapy.

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:
MeSH: Anastomosis, Surgical/adverse effects ; Anastomotic Leak/etiology ; Anastomotic Leak/prevention & control ; Animals ; Arginine/pharmacology ; Esophageal Sphincter, Lower/drug effects ; Esophageal Sphincter, Lower/pathology ; Esophageal Sphincter, Lower/physiopathology ; Esophagitis/etiology ; Esophagitis/prevention & control ; Esophagus/drug effects ; Esophagus/metabolism ; Esophagus/pathology ; Esophagus/surgery ; Male ; NG-Nitroarginine Methyl Ester/toxicity ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Peptide Fragments/pharmacology ; Pressure ; Proteins/pharmacology ; Rats, Wistar ; Stomach/drug effects ; Stomach/metabolism ; Stomach/pathology ; Stomach/surgery ; Time Factors ; Wound Healing/drug effects
Departments: Katedra za farmakologiju
Katedra za kirurgiju
Katedra za patologiju
Depositing User: Martina Žužak
Status: Published
Djaković, ŽeljkoUNSPECIFIED
Cesarec, VedranUNSPECIFIED
Madžarac, GoranUNSPECIFIED
Bečejac, TomislavUNSPECIFIED
Zukanović, GoranUNSPECIFIED
Batelja, LovorkaUNSPECIFIED
Zenko Sever, AnitaUNSPECIFIED
Kolenc, DanijelaUNSPECIFIED
Luetić, KrešimirUNSPECIFIED
Stančić-Rokotov, DinkoUNSPECIFIED
Sikirić, PredragUNSPECIFIED
Date: 7 November 2016
Date Deposited: 28 Feb 2018 11:21
Last Modified: 10 Aug 2020 08:33
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