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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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.
High hepatotoxic dose of paracetamol produces generalized convulsions and brain damage in rats. A counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736).
J Physiol Pharmacol. 2010; 61(2): 241-250.
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PubMed
- Co-authors Med Uni Graz
- Brcic Luka
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- Abstract:
- 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 microg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-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 (microg-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose.
- Find related publications in this database (using NLM MeSH Indexing)
- Acetaminophen - administration & dosage Acetaminophen - poisoning
- Analgesics, Non-Narcotic - administration & dosage Analgesics, Non-Narcotic - poisoning
- Animals -
- Anti-Ulcer Agents - administration & dosage Anti-Ulcer Agents - pharmacology
- Antidotes - administration & dosage Antidotes - pharmacology
- Brain - drug effects Brain - pathology
- Dose-Response Relationship, Drug -
- Drug Overdose -
- Hepatic Encephalopathy - chemically induced Hepatic Encephalopathy - prevention & control
- Liver Function Tests -
- Male -
- Peptide Fragments - administration & dosage Peptide Fragments - pharmacology
- Proteins - administration & dosage Proteins - pharmacology
- Rats -
- Rats, Wistar -
- Seizures - chemically induced Seizures - prevention & control
- Time Factors -
- Find related publications in this database (Keywords)
- paracetamol
- hepatic encephalopathy
- convulsions
- pentadecapeptide BPC 157
- hyperammonemia
- fatty liver