Portal de Periódicos da CAPES

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

2011; Elsevier BV; Volume: 88; Issue: 11-12 Linguagem: Inglês

10.1016/j.lfs.2011.01.015

1879-0631

Spomenko Ilić, Domagoj Drmić, Sandra Franjić, Danijela Kolenc, Marijana Ćorić, Luka Brčić, Robert Kliček, Božo Radić, Marko Sever, Viktor Djuzel, Marinko Filipović, Željko Djaković, Vasilije Stambolija, Alenka Boban Blagaić, Ivan Zoričić, Miroslav Gjurašin, Mirjana Stupnišek, Željko Romić, Kamelija Žarković, Senka Džidić, Sven Seiwerth, Predrag Sikirić,

Drug Transport and Resistance Mechanisms

We attempted to fully antagonize the extensive toxicity caused by NSAIDs (using diclofenac as a prototype). 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 (12.5 mg/kg intraperitoneally, once daily for 3 days) in rats. 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 3 h 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). 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.