Author/Editor | Ilić, Spomenko; Drmić, Domagoj; Žarković, Kamelija; Kolenc, Danijela; Coric, Marijana; Brcic, Luka; Klicek, Robert; Radic, Bozo; Sever, Marko; Djuzel, Viktor | |
Title | High hepatotoxic dose of paracetamol produces generalizedconvulsions and brain damage in rats. a counteraction with the stable gastric pentadecapeptide BPC 157 (PL 14736) | |
Type | članek | |
Vol. and No. | Letnik 61, št. 2 | |
Publication year | 2010 | |
Volume | str. 241-250 | |
ISSN | 0867-5910 - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | |
Language | eng | |
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 [micro]g, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective([micro]g-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 seizureperiod and the reafter, 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 lessliver 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 ([micro]g-ng range) as a highly effective paracetamol antidote even against highly advanced damaging processes induced by an extreme paracetamol over-dose. | |
Keywords | pentadecapeptide BPC 157 hepatic encephalopathy paracetamol pentadekapeptid BPC 157 jetrna encefalopatija paracetamol |