title: Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.
abstract: Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen.
authors.affiliation: Department of Pharmacology and Pathology Medical Faculty University of Zagreb, Zagreb, Croatia.
authors.forename: Spomenko
authors.initials: S
authors.lastname: Ilic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Drmic
authors.forename: Kamelija
authors.initials: K
authors.lastname: Zarkovic
authors.forename: Danijela
authors.initials: D
authors.lastname: Kolenc
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.forename: Bozo
authors.initials: B
authors.lastname: Radic
authors.forename: Viktor
authors.initials: V
authors.lastname: Djuzel
authors.forename: Alenka Boban
authors.initials: AB
authors.lastname: Blagaic
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Romic
authors.forename: Senka
authors.initials: S
authors.lastname: Dzidic
authors.forename: Livije
authors.initials: L
authors.lastname: Kalogjera
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
authors.forename: Predrag
authors.initials: P
authors.lastname: Sikiric
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000897:Anti-Ulcer Agents / Q000009:adverse effects / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced; D005753:Gastric Mucosa / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006529:Hepatomegaly / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D007052:Ibuprofen / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects* / Q000293:injuries / Q000473:pathology; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000897:Anti-Ulcer Agents; D010455:Peptides; D007052:Ibuprofen