engleski

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

To date paracetamol hepatic encephalopathy was not reported. After single paracetamol overdose (5 g/kg i.p.), we observed the acute hepatic toxicity throughout 24 hours, and very early, the progressive encephalopathy with severe seizures in rats. These were all counteracted by stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736) and various wound treatment, no toxicity reported) that showed a hepatoprotective effect. Materials and methods. After paracetamol (5 g/kg i.p.), ALT, AST serum values, liver and brain lesions, were assessed at 25 min, 3 and 24 hours. BPC 157 was applied (10 µg, 10 ng/kg, intraperitoneally or intragastrically) in paracetamol-rats (i) prophylactically, immediately after paracetamol or (ii) therapeutically, after 3 hours. Results. We demonstrated at 25 min post-paracetamol only increased ALT, AST serum values for the liver lesion, but significant damage in several brain areas and generalized convulsions, severe neuron loss in the hippocampus, nucleus dentatus, cortex, mesencephalon and interstitial edema of white matter. Through the next 5 hour seizure period, and thereafter, the brain and liver damage and enzyme value increase progressed, particularly throughout the 3-24h post-paracetamol period. BPC 157 consistently demonstrated clinical (no convulsions (prophylactic application) or convulsions rapidly disappeared (therapeutic effect within 25 min)), microscopical (markedly less liver and brain lesion) and biochemical (ALT, AST serum levels decreased) counteraction. Fig. 1. shows red Purkinje cells in control and Purkinje cells in BPC 157, HE x400. Conclusion. Both prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly suggest BPC 157’s role as a paracetamol antidote even against highly advanced paracetamol induced damage in liver and brain.

paracetamol; hepatic encephalopathy; pentadecapeptide BPC 157; rats

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