Influence and Implications of the Molecular Paradigm of Nitric Oxide Underlying Inflammatory Reactions of the Gastrointestinal Tract of Dog: A Major Hallmark of Inflammatory Bowel Disease

Abstract

Abstract Nitric oxide (NO), a pleiotropic free radical messenger molecule, is responsible for the various cellular function of the gastrointestinal mucosa. It plays a major role in the maintenance of perfusion, regulation of microvascular, epithelial permeability, and immune functions. Nitric oxide exerts its beneficial effect on the initiation and maintenance of inflammation in human inflammatory bowel disease (IBD). But the accelerated production of NO triggers activation of the inducible form of the NO synthase enzyme (iNOS) that leads to damages of the intestinal membrane. Nitric oxide synthase enzyme is responsible for the higher production of NO from l-arginine and causes an inflammatory condition in the intestinal epithelium. Nitric oxide induces nitrative DNA damage and oxidative DNA damage in the cellular system. Accelerated production of NO enhances iNOS activity that is associated with cytotoxicity and apoptosis of gastrointestinal epithelial cells in the dog. Chronic inflammation leads to angiogenesis that is modulated by the immune system in IBD. Chronic inflammation is a major risk factor for the development of gastrointestinal malignancies. Nitric oxide participates in mucosal inflammation in the intestine through invigoration of NO synthase enzyme. The intrinsic complex mechanism is correlated with the inflammation in the gastrointestinal tract and is also correlated with the expression of iNOS, enzymatic activity and NO production. Nitric oxide employs a significant role in modulating epithelial permeability with accelerated immune response in acute colitis. But the enormous generation of NO causes adverse effects on the mucosal cell during the inflammatory process in IBD. In this review, a complex episode of NO generation with altered biochemical pathways was assessed for the regulation of mucosal inflammation in inflammatory bowel disease of dogs. This review is a unique compilation of the role of NO in the pathogenesis of inflammatory bowel disease of dogs. Nitric oxide plays a key role in modulating cancer in the gastrointestinal tract. This review seeks to explore the characteristics of NO as a major hallmark of canine inflammatory bowel diseases.