White angico gum decreases iNOS expression in intestinal mucositis
Authors: Pimenta Helder Bindá , Menslin Kimberlly , Cunha João Luiz , Nunes João Victor , Queiroz Herdeson Araújo , Oliveira Ana Carolina , da Silva Stephany Caroline , Biason Giovanna , Alves Ronny Helson , Vidinha Alice Cristina , Lopes Matheus , Santos Victor Rodrigo , de Carvalho Vale Larice , Barbosa Maria Lucianny Lima , de Farias Sérgio Augusto , Nicolau Júlia Fernanda Alencar , Cerqueira Gilberto Santos 
Published: April 2020

The enzyme nitric oxide synthase (iNOS) is responsible for the synthesis of NO which is complemented by the conversion of L‐arginine and oxygen to L‐citrulline and NO. There are three forms of NOS identified: nitric oxide endothelial synthase (eNOS) found in the vascular endothelium, the neuronal nitric oxide synthase (nNOS) that regulates neuronal transmission, and inducible nitric oxide, first identified in macrophages. The first two are constitutive, and the last is related to tissue damage and present in inflammation and cell apoptosis (LIAUDET; SORIANO; SZABÓ, 2000; DAVIS et al., 2001).

The mechanism of action of NO can occur in two ways: when there is interaction directly with the molecule of the target system and when there is a reaction with intermediates of reactive oxygen species, which can lead to the formation of reactive nitrogen species (RNA) such as peroxynitrite. (FANG, 1997; DAVIS et al., 2001; VALKO et al., 2007). Intestinal mucositis was induced in mice with the administration of 5 FU, according to the methodology described by Carneiro‐Filho et al. (2004), adapted. The treatment was done using three doses of angico branco gum (100, 200, 400 mg/kg) one day after i.p. of 5‐FU, the choice of doses being based on the study by Santos et al. (2013). The other groups received saline.

Suppression of NO is an essential indicator for the development of an anti‐inflammatory agent, since NO is a mediator of inflammation derived from pro‐inflammatory cytokines and produced in various inflammatory conditions resulting from cytokine cytotoxicity (KHAN et al., 2015; TOSUN et al., 2014; CHUN et al., 2012). It has also been shown that NO negatively regulates the expression of adhesion molecules in the vascular endothelium, thus decreasing neutrophil trafficking in inflamed tissues (LEITÃO et al., 2006).

When investigating the possible involvement of nitric oxide in the protective effect of white angico gum on morphometric and histopathological changes in mice submitted to intestinal mucositis by 5‐FU, it was evaluated that the administration of L‐NAME with white angico gum, as well as the separate administration of the two compounds prevented the villus shortening caused by 5‐FU, and increased the villus/crypt ratio. Thus, it can be said that both individual, and acting synergistically blocked the effects of NO and, consequently, can be used to treat intestinal mucositis. In conclusion, we observed that the angico gum at a concentration of 400 mg/kg had a protective effect on the intestinal mucosa, after inducing injury by chemotherapy, by decreasing the immunostaining for the enzyme iNOS, demonstrating the role of antiinflammatory.

GAB = 400mg/kg white angico gum. Values were expressed as mean ± SEM of the percentage of the immunostained area for INOS.

Figure 1