title: Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model: diclofenac-induced gastrointestinal, liver, and encephalopathy lesions.
abstract: OBJECTIVE
  We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype).
  
  
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmacology and Pathology Medical Faculty, University of Zagreb, Zagreb, Croatia.
authors.forename: Spomenko
authors.initials: S
authors.lastname: Ilic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Sandra
authors.initials: S
authors.lastname: Franjic
authors.forename: Danijela
authors.initials: D
authors.lastname: Kolenc
authors.forename: Marijana
authors.initials: M
authors.lastname: Coric
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Robert
authors.initials: R
authors.lastname: Klicek
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Marko
authors.initials: M
authors.lastname: Sever
authors.forename: Viktor
authors.initials: V
authors.lastname: Djuzel
authors.forename: Marinko
authors.initials: M
authors.lastname: Filipovic
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Djakovic
authors.forename: Vasilije
authors.initials: V
authors.lastname: Stambolija
authors.forename: Alenka Boban
authors.initials: AB
authors.lastname: Blagaic
authors.forename: Ivan
authors.initials: I
authors.lastname: Zoricic
authors.forename: Miroslav
authors.initials: M
authors.lastname: Gjurasin
authors.forename: Mirjana
authors.initials: M
authors.lastname: Stupnisek
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Romic
authors.forename: Kamelija
authors.initials: K
authors.lastname: Zarkovic
authors.forename: Senka
authors.initials: S
authors.lastname: Dzidic
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004008:Diclofenac; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006501:Hepatic Encephalopathy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D011506:Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D010446:Peptide Fragments; D011506:Proteins; D004008:Diclofenac; C083833:BPC 157