Role of Nitric Oxide in Gastrointestinal Inflammatory and Ulcerative Diseases: Perspective for Drugs Development

Abstract

Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constitutive synthesis of NO by nNOS or eNOS isoforms is involved in the maintaining of the gastrointestinal mucosal integrity through modulation of gastric mucosal blood flow, epithelial secretion and barrier function. However, large amounts of NO synthesized from the inducible isoform have been implicated in tissue injury in the gut during inflammatory reactions. In this review we provide an overview of the dual role of nitric oxide in modulating gastrointestinal mucosal defense and injury. In addition, we highlight the therapeutic potential of NO modulation.

On the benefits of silymarin in murine colitis by improving balance of destructive cytokines and reduction of toxic stress in the bowel cells

“…Also, other investigations have shown an increase in its levels in the colonic samples of animals with TNBS-induced colitis. Results of the TBARS assay in colonic tissue revealed that silymarin attenuates colonic damage by down-regulating the lipid peroxidation process, confirming previous findings on the anti-oxidant properties of silymarin [26,33]. It likely exerts this effect through its ability to antagonize free radical production and activity, and maintaining a balance between oxidants and anti-oxidants.…”

“…Many researches have shown that constitutive production of NO from endothelial NO synthase (eNOS) is advantageous in acute colitis, although chronic overproduction of NO from iNOS is associated with perpetuation of inflammatory process [32][33][34]. Furthermore, silymarin diminishes the release of proinflammatory cytokines like IL-1, IL-6, interferon (IFN)-γ and TNF-α from activated immune cells and consequently lessens activation of other immune cells following their release [27].…”

Protective effect of Acer mono Max. sap on water immersion restraint stress-induced gastric ulceration

“…Large amounts of iNOS-induced NO have been identified in gastric tissue damage during inflammatory processes (34), and high levels of iNOS expression and activity have been related to severe inflammation in ulcerative mucosal cells (35). Studies have revealed that iNOS is usually induced under oxidative reactions, wherein high levels of NO reacts with the superoxide anion, thus causing peroxynitrite generation, tyrosine-mediated nitration, hydroxyl radical production, cellular toxicity and tissue lesions (35,36).…”

Óxido nítrico: revisão

“…A atividade do NO foi relatada em endotélio, cerebelo, nervos não adrenérgicos não colinérgicos (NANC), macrófagos, neutrófilos, rins, células epiteliais pulmonares, mucosa gastrintestinal e miocárdio 6,[25][26][27][28] . O NO também pode ser responsável pela vasodilatação presente na angiogênese fisiológica ou patológica, como no caso de tumores 29 .…”