Effects of diclofenac, L-NAME, L-Arginine, and pentadecapeptide BPC 157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 hour-short-bowel rats

Lojo, Nermin and Rašić, Žarko and Zenko Sever, Anita and Kolenc, Danijela and Vukušić, Darko and Drmić, Domagoj and Zoričić, Ivan and Sever, Marko and Seiwerth, Sven and Sikirić, Predrag (2016) Effects of diclofenac, L-NAME, L-Arginine, and pentadecapeptide BPC 157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 hour-short-bowel rats. PLoS ONE, 11 (9). e0162590. ISSN 1932-6203

[img] PDF - Published Version
Download (4MB)


Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.

Item Type: Article
Additional Information: © 2016 Lojo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MeSH: Anastomosis, Surgical/adverse effects ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Arginine/pharmacology ; Brain/drug effects ; Diclofenac/adverse effects ; Diclofenac/pharmacology ; Gastrointestinal Tract/drug effects ; Intestine, Small/drug effects ; Intestine, Small/surgery ; Liver/drug effects ; Male ; NG-Nitroarginine Methyl Ester/pharmacology ; Peptide Fragments/pharmacology ; Proteins/pharmacology ; Rats ; Rats, Wistar ; Wound Healing/drug effects
Departments: Katedra za farmakologiju
Katedra za patologiju
Depositing User: Martina Žužak
Status: Published
Zenko Sever, AnitaUNSPECIFIED
Kolenc, DanijelaUNSPECIFIED
Sikirić, PredragUNSPECIFIED
Date: 14 September 2016
Date Deposited: 04 Oct 2017 09:46
Last Modified: 11 Aug 2020 08:43
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2688

Actions (login required)

View Item View Item


Downloads per month over past year