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Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model : Diclofenac-induced gastrointestinal, liver, and encephalopathy lesions (CROSBI ID 176950)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Ilić, Spomenko ; Drmić, Domagoj ; Franjić, Sandra ; Kolenc, Danijela ; Ćorić, Marijana ; Brčić, Luka ; Kliček, Robert ; Radić, Božo ; Sever, Marko ; Đuzel, Viktor et al. Pentadecapeptide BPC 157 and its effects on a NSAID toxicity model : Diclofenac-induced gastrointestinal, liver, and encephalopathy lesions // Life sciences, 88 (2011), 11-12; 535-542. doi: 10.1016/j.lfs.2011.01.015

Podaci o odgovornosti

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

engleski

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

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. 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 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.

BPC 157 ; diclofenac ; NSAIDs ; toxicity ; rats

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Podaci o izdanju

88 (11-12)

2011.

535-542

objavljeno

0024-3205

1879-0631

10.1016/j.lfs.2011.01.015

Povezanost rada

nije evidentirano

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