Effect of a Cytoprotective Dose of Dehydroleucodine, Xanthatin, and 3-Benzyloxymethyl-5H-furan-2-one on Gastric Mucosal Lesions Induced by Mast Cell Activation.

Mariano Ezequiel Vera,Alicia Beatriz Penissi,María Laura Mariani,Cristina Aguilera

doi:10.3390/ijms22115983

Abstract

The aim of this study was to determine whether the lactones dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one, would be effective in an animal model of gastric ulcer induced by mast cell activation. Rats were divided into ten groups. Treatments were repeated for four days. The degree of gastric erosion was assessed with a scoring system and histological preparations. Gastric mast cell morphology was analyzed by histological procedures. Serum serotonin levels were determined as markers of mast cell activation. Statistical analyses were done using ANOVA and Tukey–Kramer test. We demonstrated that the repeated administration of compound 48/80 results in extensive mucosal lesions in the gastric mucosa and that such lesions occurred in association with mast cell degranulation and a significant increase of serum serotonin. We showed that these lesions were prevented by dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one and that this effect was similar to that obtained with sodium cromoglycate. In conclusion, the results of the present study indicate that the optimal gastric cytoprotective dose of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one is efficacious in an animal model of gastric ulcer induced by mast cell activation. Our findings suggest that these lactones could be valuable tools for designing novel therapeutic agents for digestive disorders associated with inappropriate mast cell activation.

Highlights

Published: 1 June 2021Gastric ulcer disease is a major chronic digestive disorder affecting millions of people worldwide and being one of the leading causes of morbidity and mortality [1]
The term in vivo directly indicates the evaluation of drugs in a living organism, and evaluation of antiulcer drugs is incomplete without using an in vivo model because the gastric ulcer is a disease that occurs in the body’s internal environment and forms lesions in humans
We have demonstrated that the potency of dehydroleucodine, xanthatin, and 3-benzyloxymethyl-5H-furan-2-one was higher than that of ketotifen and sodium cromoglycate to inhibit mast cell serotonin release from rat peritoneal mast cells induced by compound 48/80 [25,26]

Summary

Introduction

Gastric ulcer disease is a major chronic digestive disorder affecting millions of people worldwide and being one of the leading causes of morbidity and mortality [1]. It is the result of an imbalance between endogenous protective factors of the gastric mucosa and aggressive factors [2,3]. This condition is characterized by discontinuation in the stomach mucosa lining because of gastric acid or pepsin secretion induced by different types of triggers. Effective treatment for this condition and its complications remains a significant therapeutic challenge at present [7]

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Conclusion