Effect of N-palmitoylethanolamine-oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease.

Abstract

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal (GI) tract, and it is associated with different neurological disorders. Recent evidence has demonstrated that the gut-brain-axis has a central function in the perpetuation of IBS, and for this reason, it can be considered a possible therapeutic target. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects on the gut-brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA-OXA on the gut-brain axis in rats subjected to experimental colitis induced by oral administration of dextran sulfate sodium (DSS). Daily oral administration of PEA-OXA (10 mg/kg daily o.s.) was able to decrease the body weight loss, macroscopic damage, colon length, histological alteration, and inflammation after DSS induction. Additionally, PEA-OXA administration enhanced neurotrophic growth factor release and decreased the astroglial and microglial activation induced by DSS. Moreover, PEA-OXA restored intestinal permeability and tight junctions (TJs) as well as reduced apoptosis in the colon and brain. In our work, we demonstrated, for the first time, the action of PEA-OXA on the gut-brain axis in a model of DSS-induced colitis and its implication on the "secondary" effects associated with colonic disturbance.

• Authors: Marika Cordaro, Maria Scuto, Rosalba Siracusa, Ramona D'amico, Alessio Filippo Peritore, Enrico Gugliandolo, Roberta Fusco, Rosalia Crupi, Daniela Impellizzeri, Michele Pozzebon, Daniele Alfonsi, Nicolò Mattei, Gabriele Marcolongo, Maurizio Evangelista, Salvatore Cuzzocrea, Rosanna Di Paola
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 34 Issue 3 Pg. 4085-4106 (03 2020) ISSN: 1530-6860 [Electronic] United States
• PMID: 31950563 (Publication Type: Journal Article)
• Copyright: © 2020 Federation of American Societies for Experimental Biology.

Chemical References

• Aif1 protein, rat
• Amides
• Calcium-Binding Proteins
• Ethanolamines
• GFAP protein, rat
• Glial Cell Line-Derived Neurotrophic Factor
• Glial Fibrillary Acidic Protein
• ICAM1 protein, rat
• Microfilament Proteins
• Oxazoles
• P-Selectin
• Palmitic Acids
• Intercellular Adhesion Molecule-1
• palmidrol
• Dextran Sulfate

Topics

• Amides (therapeutic use)
• Animals
• Body Weight (drug effects)
• Calcium-Binding Proteins (metabolism)
• Dextran Sulfate (toxicity)
• Ethanolamines (therapeutic use)
• Glial Cell Line-Derived Neurotrophic Factor (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Humans
• Immunohistochemistry
• Inflammatory Bowel Diseases (chemically induced, drug therapy, metabolism)
• Intercellular Adhesion Molecule-1 (metabolism)
• Male
• Microfilament Proteins (metabolism)
• Oxazoles (therapeutic use)
• P-Selectin (metabolism)
• Palmitic Acids (therapeutic use)
• Rats
• Rats, Sprague-Dawley