Abstract
IBD (Inflammatory Bowel Disease) is an inflammatory disease affecting the gastrointestinal tract that is common in both humans and veterinarians. Several studies have revealed the pharmacological properties of the oxazoline of palmitoylethanolamide (PEAOXA). Zebrafish larvae were exposed to sodium dextran sulphate (DSS) to induce enterocolitis and study the protective action of PEAOXA. After repetitive exposure with 0.25% DSS, larvae presented gut alteration with an increase in mucus production. Furthermore, DSS exposure induced an increase in the inflammatory pathway in the intestine, related to an increase in the Endoplasmic-reticulum (ER) stress genes. PEAOXA exposure at a concentration of 10 mg/L decreased the DSS-induced gut damage and mucus production, as well as being able to reduce the inflammatory and ER stress-related genes expression. In conclusion, our results demonstrate that the alterations induced by repeated exposure to DSS were counteracted by PEAOXA action that was able to inhibit the increase in inflammation and ER stress involved in the progression of enterocolitis.
Highlights
Introduction published maps and institutional affilThe inflammatory response, when properly regulated, helps to maintain cellular homeostasis and resistance to disease, but its persistence, i.e., chronic inflammation, can lead to autoimmune disorders related to various diseases, such as diabetes, neurodegenerative diseases, asthma or arthritis [1].While murine inflammatory bowel disease (IBD) models are useful for elucidating disease pathogenesis they are prohibitively expensive to use for in vivo drug screening.Zebrafish embryos were previously assessed as models of chemically-induced enterocolitis and IBD and potentially provide a low-cost animal model of acute colitis for antiinflammatory drug development programs in the early phases [2,3]
The histopathological examination of the zebrafish intestinal sections after haematoxylin and eosin (H&E) staining was performed to assess the protective effect of PEAOXA on the mild intestine morphology after DSS treatment
Zebrafish repetitively exposed to DSS caused tissue inflammation as well as major pathological alterations such as severe epithelium damage and an increase in the number of goblet cells (Figure 1)
Summary
Introduction published maps and institutional affilThe inflammatory response, when properly regulated, helps to maintain cellular homeostasis and resistance to disease, but its persistence, i.e., chronic inflammation, can lead to autoimmune disorders related to various diseases, such as diabetes, neurodegenerative diseases, asthma or arthritis [1].While murine inflammatory bowel disease (IBD) models are useful for elucidating disease pathogenesis they are prohibitively expensive to use for in vivo drug screening.Zebrafish embryos were previously assessed as models of chemically-induced enterocolitis and IBD and potentially provide a low-cost animal model of acute colitis for antiinflammatory drug development programs in the early phases [2,3]. The inflammatory response, when properly regulated, helps to maintain cellular homeostasis and resistance to disease, but its persistence, i.e., chronic inflammation, can lead to autoimmune disorders related to various diseases, such as diabetes, neurodegenerative diseases, asthma or arthritis [1]. While murine inflammatory bowel disease (IBD) models are useful for elucidating disease pathogenesis they are prohibitively expensive to use for in vivo drug screening. Zebrafish embryos were previously assessed as models of chemically-induced enterocolitis and IBD and potentially provide a low-cost animal model of acute colitis for antiinflammatory drug development programs in the early phases [2,3]. Zebrafish use the proximal intestine (PI) for food storage and mixing, as they lack a stomach [4,5]. The middle intestine (MI) of the zebrafish is composed of enterocytes, which are responsible for nutrient absorption, and goblet cells that produce mucin.
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