High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736)

• Autorzy: Ilic S. , Drmic D. , Zarkovic K. , Kolenc D. , Coric M. , Brcic L. , Klicek R. , Radic B. , Sever M. , Djuzel V. , Ivica M. , Boban Blagaic A. , Zoricic Z. , Anic T. , Zoricic I. , Djidic S. , Romic Z. , Seiwerth S. , Sikiric P.
• Języki publikacji: EN

Abstrakty

EN

We focused on stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported) because of its hepatoprotective effects. We investigate a particular aspect of the sudden onset of encephalopathy with extreme paracetamol overdose (5 g/kg intraperitoneally) so far not reported: rapidly induced progressive hepatic encephalopathy with generalized convulsions in rats. BPC 157 therapy (10 µg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (µg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). At 25 min post-paracetamol increased ALT, AST and ammonium serum values precede liver lesion while in several brain areas, significant damage became apparent, accompanied by generalized convulsions. Through the next 5 hour seizure period and thereafter, the brain damage, liver damage enzyme values and hyperammonemia increased, particularly throughout the 3-24 h post-paracetamol period. BPC 157 demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesions) and biochemical (enzyme and ammonium serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 (µg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.

Słowa kluczowe

EN

brain damage; convulsion; fatty liver; hepatic encephalopathy; hyperammonemia; inflammatory bowel disease; paracetamol; pentadecapeptide BPC 157; rat

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 2010
• Tom: 61
• Numer: 2
• Opis fizyczny: p.241-250,fig.,ref.

Twórcy

autor

Ilic S.

• Medical Faculty University of Zagreb, 11 Salata Street, POB 916, 10000 Zagreb, Croatia

autor

Drmic D.

autor

Zarkovic K.

autor

Kolenc D.

autor

Coric M.

autor

Brcic L.

autor

Klicek R.

autor

Radic B.

autor

Sever M.

autor

Djuzel V.

autor

Ivica M.

autor

Boban Blagaic A.

autor

Zoricic Z.

autor

Anic T.

autor

Zoricic I.

autor

Djidic S.

autor

Romic Z.

autor

Seiwerth S.

autor

Sikiric P.

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