A L-glutamina e o óxido nítrico promovem a plasticidade das células intersticiais de Cajal em ratos portadores de Tumor de Walker-256

Abstract

Interstitial cells of Cajal (ICC) provides a mechanism to control the peristalsis of the gastrointestinal (GI) tract. In outer longitudinal muscle layer, near the myenteric plexus (MY), ICC-MY form a three-dimensional network, with function to generating and propagating slow waves in the muscles. In inner circular muscle layer, near the deep muscular plexus (DMP), ICC-DMP are presented in loose networks with fine processes, with function to signal neurotransmission. The transmembrane protein Ano1, participates in the regulation of Ca2+ and Cl- channels, and presents specific and high expression in the CIC and is used to show of the same. Nitric oxide (NO) appears to be involved in the survival of these cells. Cancer cachexia promotes the increase of inflammatory processes and oxidative stress, which can lead to abnormalities in intestinal motility. Substances with antioxidant action, participating in the reduction of oxidative stress, can prevent the damage caused by the tumor. L-glutamine is an amino acid involved indirectly in increasing skeletal muscle protein synthesis and precursor of glutathione. Therefore the aim of the present study was to investigate the effects of supplementation with L-glutamine to 2% on the networks of ICC-MY and ICC-DMP and on neuronal nitric oxide synthase (nNOS, type I). Rattus norvegicus Wistar males with 57 days of age were divided into four groups: control (C), control supplemented with L-glutamine (CG), with Walker-256 tumor (WT), Walker-256 tumor patients supplemented with L-glutamine (WTG). After 14 days of supplementation, jejunums were collected and processed for immunohistochemical techniques whole-mount and cryosections prepared, and Western blot analysis. Quantitative analyzes were performed to Ano1 and nNOS. The reduced density of ICC and the increase in Ano1 protein expression was observed in the WT group compared to the C group (p <0.05). Reduction in density can be related to oxidative stress, which is high in cancer. Greater production of nitric oxide (NO) stimulated proliferation and maintenance of ICC-DMP network. Cachexia was lower in the WTG group compared to WT (p <0.05). Supplementation with L-glutamine increases protein synthesis by preventing the development of cachexia. L-glutamine in the WTG group promoted high plasticity in ICC, due to its antioxidant action. The repair mechanisms of ICC have not been explained, but it is possible to deduce that L-glutamine may be involved in the regulation of Ca+2 e Cl- channels. NO can interact with the ICC, and, together with the antioxidant treatment appear to contribute to the protection and repair of these cells, maintaining intestinal homeostasis in the Walker-256 tumor model.