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Ibuprofen, Hepatic Encephalopathy, Hepatomegaly, Gastric Lesion and Gastric Pentadecapeptide BPC157 in Rats

Stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419) is an orally active anti-ulcer peptide that may also have an effect on many central disturbances, efficient in inflammatory bowel disease trials (PL14736) and various wound treatment, no toxicity reported, which showed various hepatoprotective effects. Therefore, we challenged rats with chronic ibuprofen application (0.4g/kg intraperitoneally once daily for 4 weeks) and BPC 157 therapy. We evidenced a deleterious circuit not reported in ibuprofen-rats as yet: hepatic encephalopathy, gastric lesions, hepatomegaly (Fig.1, C (control) B (BPC 157)), increased AST and ALT serum values, with prolonged sedation/unconsciousness and weight loss. In particular, ibuprofen toxicity exhibited itself as brain edema and cyanosis, particularly in the cerebellum, more so in white than in gray mater, damaged (balonized) red neurons, without any inflammatory reaction, particularly in the cerebral cortex and cerebellar nuclei (Fig. 1), less in the hippocampus, dentate nucleus and Purkinje cells. BPC 157 ( 10μg, 10ng/kg) was fully effective given as an antidote after ibuprofen: (i) intraperitoneally, immedi- ately after ibuprofen or (ii) in drinking water (0.16 μg, 0.16 ng/ml) until the end of the 4 week-experiment. Thus, apart from its role as an anti-ulcer peptide, efficient in inflammatory bowel disease trials (PL14736) and various wound treatment, with no toxicity reported and which already showed various hepatoprotective effects, either BPC 157 regimen counteracted all of ibuprofen's adverse effects, such as hepatic encephalopathy, gastric lesions, hepatomegaly, increased liver serum values, and BPC 157 rats showed no behavioral disturbances and maintained normal weight gain.

Ibuprofen; hepatic encephalopathy; hepatomegaly; gastric lesion; BPC 157; rats

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