Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats

详细信息    查看全文

• 作者：Spomenko Ilic ; Domagoj Drmic ; Kamelija Zarkovic ; Danijela Kolenc ; Luka Brcic ; Bozo Radic ; Viktor Djuzel ; Alenka Boban Blagaic ; Zeljko Romic ; Senka Dzidic ; Livije Kalogjera ; Sven Seiwerth ; Predrag Sikiric ; ^{sikiric@mef.hr}
• 关键词：Ibuprofen ; Hepatic encephalopathy ; Hepatomegaly ; Sedation/unconsciousness ; Gastric lesion ; Pentadecapeptide BPC 157 ; Rat
• 刊名：European Journal of Pharmacology
• 出版年：2011
• 出版时间：30 September, 2011
• 年：2011
• 卷：667
• 期：1-3
• 页码：322-329
• 全文大小：1K

文摘

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 ¦Ìg, 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 ¦Ìg, 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.