Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.

Abstract

AIMS:

We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype).

MAIN METHODS:

Herein, we used the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419), an anti-ulcer peptide shown to be efficient in inflammatory bowel disease clinical trials (PL 14736) and various wound treatments with no toxicity reported. This peptide was given to antagonize combined gastrointestinal, liver, and brain toxicity induced by diclofenac (12.5mg/kg intraperitoneally, once daily for 3 days) in rats.

KEY FINDINGS:

Already considered a drug that can reverse the toxic side effects of NSAIDs, BPC 157 (10 μg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/mL, 0.16 ng/mL). Without BPC 157 treatment, at 3h following the last diclofenac challenge, we encountered a complex deleterious circuit of diclofenac toxicity characterized by severe gastric, intestinal and liver lesions, increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally hepatic encephalopathy (brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly in the hippocampal neurons).

SIGNIFICANCE:

The very extensive antagonization of diclofenac toxicity achieved with BPC 157 (μg-/ng-regimen, intraperitoneally, per-orally) may encourage its further use as a therapy to counteract diclofenac- and other NSAID-induced toxicity.

• Authors: Spomenko Ilic, Domagoj Drmic, Sandra Franjic, Danijela Kolenc, Marijana Coric, Luka Brcic, Robert Klicek, Bozo Radic, Marko Sever, Viktor Djuzel, Marinko Filipovic, Zeljko Djakovic, Vasilije Stambolija, Alenka Boban Blagaic, Ivan Zoricic, Miroslav Gjurasin, Mirjana Stupnisek, Zeljko Romic, Kamelija Zarkovic, Senka Dzidic, Sven Seiwerth, Predrag Sikiric
• Journal: Life sciences (Life Sci) Vol. 88 Issue 11-12 Pg. 535-42 (Mar 14 2011) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 21295044 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Anti-Ulcer Agents
• Peptide Fragments
• Proteins
• Diclofenac
• BPC 157

Topics

• Administration, Oral
• Animals
• Anti-Inflammatory Agents, Non-Steroidal
• Anti-Ulcer Agents (administration & dosage, therapeutic use)
• Behavior, Animal (drug effects)
• Chemical and Drug Induced Liver Injury (etiology, pathology, prevention & control)
• Diclofenac
• Disease Models, Animal
• Gastric Mucosa (drug effects, pathology)
• Gastrointestinal Diseases (chemically induced, pathology, prevention & control)
• Hepatic Encephalopathy (etiology, pathology, prevention & control)
• Injections, Intraperitoneal
• Intestinal Mucosa (drug effects, pathology)
• Liver Function Tests
• Male
• Peptide Fragments (administration & dosage, therapeutic use)
• Proteins (administration & dosage, therapeutic use)
• Rats
• Rats, Wistar