Potassium Channel Openers and Improvement of Toxic Stress: Do they have Role in the Management of Inflammatory Bowel Disease?

Azadeh      Hosseini-Tabatabaei; Mohammad      Abdollahi

doi:10.2174/187152808785748164

Abstract

Inflammatory bowel disease (IBD) is a progressive condition in gastrointestinal tract, which refers to two idiopathic diseases; ulcerative colitis and Crohns disease. Although certain etiology of these conditions is not known, it seems that an abnormality in reaction and regulation of the immune system plays an important role in adventure of the disease. According to the investigations, it is likely that oxidative and nitrosative stress have etiologic roles in IBD. Their destructive effects may contribute to the initiation or progression of the disease. Nowadays, the effectiveness of different medicines in the treatment of IBD has been proved, but none of them has shown a desirable result. Potassium channel openers (PCOs) are a class of drugs with various usages in the aspects of cardiovascular diseases and urinary incontinence. Their major mechanism is the opening of ATP-sensitive potassium (K-ATP) channels and contribute to the relaxation of smooth muscles. Nicorandil is a member of PCOs, with a special chemical structure. Recent investigations mention some novel effects and functions for this drug. Nicorandil reveals an anti-apoptosis property not only via a nitric oxide (NO)/cGMPdependent mechanism, but also through activating mitochondrial K-ATP channels. Nicorandil can also elevate cGMP levels in some tissues, without direct NO generation. Gastroprotective activity via opening of the K channels, free radical scavenging, prostaglandin E2 elevation, decreasing pepsin and acid secretion, and prevention of the detrimental rise in NO has been proposed for nicorandil. According to these protective mechanisms and the role of oxidative/nitrosative stress in the expression of IBD, we herein hypothesize that nicorandil and other PCOs with similar structure can be used in the management of IBD. This approach offers new hope for the successful treatment of IBD. Further investigations on animal models are needed, to place nicorandil and similar drugs alongside IBD therapy.

Keywords: Inflammatory bowel disease (IBD), Potassium Channel Openers (PCOs), ulcerative colitis, Crohn's disease, immune system, cardiovascular diseases, urinary incontinence, anti-apoptosis, oxidative/nitrosative stress