Glycomacropeptide Ameliorates Indomethacin-Induced Enteropathy in Rats by Modifying Intestinal Inflammation and Oxidative Stress.

Daniel Cervantes-García,Armida I Bahena-Delgado,María C Martínez-Saldaña,Mariela Jiménez,Eva Salinas,Vanessa Ruiz-Esparza Palacios,Laura E Córdova-Dávalos,Esperanza Sánchez-Alemán

doi:10.3390/molecules25102351

Abstract

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-1β 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.

Highlights

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of medicines widely indicated to treat inflammation and pain in rheumatic and musculoskeletal disorders, like rheumatoid arthritis and osteoarthritis [1]
6.37-fold factor involved in neutrophil recruitment [41], we investigated the mRNA expression level of this higher in INDO-administered than in the control groupinfiltration, (p < 0.001), thatthat treatment chemokine in mucosal tissue
In this study we investigated whether GMP, a bioactive peptide obtained from milk κ-casein, may protect against enteropathy induced by indomethacin

Summary

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of medicines widely indicated to treat inflammation and pain in rheumatic and musculoskeletal disorders, like rheumatoid arthritis and osteoarthritis [1]. 30 million people consume NSAIDs every day [2]. These anti-inflammatory drugs inhibit prostaglandin (PG) synthesis by preventing arachidonic acid (AA) from binding to the active site of cyclooxygenase (COX) enzymes [3]. Two isoforms of COX are involved in the initial steps of PG synthesis under different conditions. The expression of the COX-2 isoform is induced once inflammation is established, leading to increased production of proinflammatory PGs [4]. The COX-1 isoform is constitutively expressed in the gastrointestinal tract, kidney and platelets, participating in their homeostasis and proper function

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