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Molecules ; 25(10)2020 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-32443501

RESUMEN

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy is considered a serious and increasing clinical problem without available treatment. Glycomacropeptide (GMP) is a 64-amino acid peptide derived from milk κ-casein with numerous biological activities. The aim of this study was to investigate the protective effect of GMP on NSAID enteropathy in rats. Enteropathy was induced by seven days oral indomethacin administration. Rats were orally GMP treated from seven days previous and during the establishment of the enteropathy model. Changes in metabolism, hematological and biochemical blood alterations, intestinal inflammation and oxidative damage were analyzed. Integrity barrier markers, macroscopic intestinal damage and survival rate were also evaluated. GMP treatment prevented anorexia and weight loss in animals. Furthermore, prophylaxis with GMP ameliorated the decline in hemoglobin, hematocrit, albumin and total protein levels. The treatment had no therapeutic efficacy on the decrease of occludin and mucin (MUC)-2 expression in intestinal tissue. However, GMP markedly decreased neutrophil infiltration, and CXCL1, interleukin-1ß and inducible nitric oxide synthase expression. Nitric oxide production and lipid hydroperoxide level in the small intestine were also diminished. These beneficial effects were mirrored by preventing ulcer development and increasing animal survival. These results suggest that GMP may protect against NSAID enteropathy through anti-inflammatory and antioxidant properties.


Asunto(s)
Caseínas/química , Inflamación/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/química , Enteropatías Perdedoras de Proteínas/tratamiento farmacológico , Animales , Caseínas/farmacología , Quimiocina CXCL1/genética , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Indometacina/toxicidad , Inflamación/inducido químicamente , Inflamación/complicaciones , Inflamación/patología , Interleucina-1beta/genética , Mucosa Intestinal , Proteínas de la Leche/química , Proteínas de la Leche/farmacología , Mucina 2/genética , Óxido Nítrico Sintasa de Tipo II/genética , Fragmentos de Péptidos/farmacología , Enteropatías Perdedoras de Proteínas/inducido químicamente , Enteropatías Perdedoras de Proteínas/complicaciones , Enteropatías Perdedoras de Proteínas/genética , Ratas
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