High hepatotoxic dose 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 with generalized convulsions was not reported in rats. After a single paracetamol overdose (5g/kg intraperitoneally), an acute hepatic toxicity and a progressive encephalopathy with severe seizures and a very early onset, appeared in rats. These were all counteracted by the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, an anti-ulcer peptide efficient in inflammatory bowel disease trials (PL 14736), no toxicity reported), which showed hepatoprotective effects. After paracetamol, BPC 157 was applied (10µ ; ; g, 10ng/kg, intraperitoneally or intragastrically) (i)prophylactically, immediately after or (ii)therapeutically, after 3 hours elapsed. At 25 min post-paracetamol only ALT and AST serum values increased for the liver lesion, but 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 and enzyme values increased, particularly throughout the 3h-24h 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 serum levels decreased) counteraction. Both, the prophylactic and therapeutic benefits (intraperitoneally and intragastrically) clearly imply BPC 157 as a paracetamol antidote even against highly advanced damaging processes induced by paracetamol.