Angico Gum suppresses inflammatory responses and maintains tissue integrity through the NO and COX‐2 pathway in intestinal mucositis induced by 5‐fluorouracil

Abstract

Intestinal homeostasis has often been referred to as a state of controlled inflammation, in which pro‐ and anti‐inflammatory factors function in a synchronous manner. In this context, intestinal mucositis can be deemed as an inflammatory pathophysiological process, which results in morphological and physiological changes in the intestinal mucosa of the gastrointestinal tract. Its emergence is due to the administration of antineoplastic agents, such as 5‐fluorouracil (5‐FU), an antimetabolite, during cancer therapy (1). With high rates of morbidity and mortality, mucositis still represents an obstacle in the treatment of cancer due to the lack of an effective treatment. Numerous studies have explored natural products and secondary metabolites from medicinal plants such as natural gums to find compounds having pharmacological activity against various human health disorders. Angico (Anadenanthera colubrina (Vell.)) is a plant of the Fabaceae family prevalent in the Brazilian ecosystems of the Cerrado and Caatinga (4). Angico has been reported to possess medicinal properties for the treatment of diarrhea, cough, bronchitis, and inflammation (5). Secondary metabolites such as steroids, flavonoids, terpenes, andphenolic derivatives can be extracted from the bark of A. colubrina (6) that can function as antioxidants, antimicrobials, and anti‐inflammatory, anti‐proliferative, antiallergic, antithrombotic, and antiviral agents (7). In the present study, we aimed to evaluate the effect of AG on experimental intestinal mucositis induced by 5‐FU. Swiss mice were randomly divided into nine groups: Saline, 5‐FU, AG‐100, AG‐400, Celecoxib (CLX), CLX + AG‐400, L‐NAME, L‐Arginine, and AG + L‐NAME. The animals were euthanized, then, blood and segments of the small intestine were collected to evaluate histopathological, levels of malondialdehyde (MDA) and Nitrite/Nitrate (NOx), leukocytes, mast and goblet cell counts, and immunohistochemical analysis of induced nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2). AG prevents morphofunctional changes in experimental intestinal mucositis due to 5‐FU by attenuating inflammation, oxidative stress, tissue damage, mastocytosis, and leukopenia. These results suggest that the NO and COX‐2 pathways are possible mechanisms mediating the protective effect of AG on intestinal mucositis induced by antineoplastic chemotherapeutic agents such as 5‐FU.