Transplantologiya 2014

Key words: small intestine, ischemia/reperfusion, enzymes-antioxidants.
Introduction

The small intestine is the most vulnerable among the visceral organs to an ischemia-reperfusion (I/R) injury. The mucosa of the small intestine consists of cells that are easily damaged in ischemia. The subsequent restoration of blood flow in the ischemic gut, i.e. reperfusion, leads to a further mucosal damage. I/R injury may occur in a variety of situations, such as an intestinal transplantation, neonatal necrotizing enterocolitis, strangulated hernia, hypovolemic/septic shock, and others [1].

Still poorly understood are the changes that take place in the small intestine following the blood flow restoration after the resolution of strangulation ileus. A strangulated small bowel obstruction is especially dangerous since it is associated with blood circulation impairments in the mesenteric and intestinal wall vessels due to their compression. Many investigators have noted that a postoperative blood flow restoration in the ischemic intestine makes the onset of all pathomorphological changes both in the gut and in the whole body [2-5].

The ischemia/reperfusion is mainly considered as a complex two-staged process when the impairments arising from acute ischemia are exacerbated and often become irreversible after the restoration of the blood flow in an organ [6]. During ischemia, the mitochondrial synthesis of adenosine triphosphate (ATP) discontinues, and a rapid decrease of creatine phosphate, and of ATP later on, occurs in cells. High-energy phosphates degrade to adenosine that is metabolized to inosine and hypoxantine [7]. A hypoxic stress triggers the conversion of xanthine dehydrogenase to xanthine oxidase that generates oxygen free radicals. The restoration of the blood flow in an ischemic organ initiates a cascade of events leading to an additional damage of the organ mucosa. During the reperfusion, the molecular oxygen penetrates into tissues where it interacts with hypoxanthine and xanthine oxidase. This leads to a "burst" in the production of oxygen free radicals such as superoxide anion (O₂^-), and hydrogen peroxide (H₂O₂) [8].

Thus, the reperfusion in the ischemia-affected intestine may give rise to a powerful oxidative stress and a subsequent destruction of the intestinal epithelium due to a massive cell death. Meanwhile, a pharmacological modulation of the reperfusion may improve the functional integrity of the intestinal tissue and subsequent clinical course.

Currently anti-oxidant enzymes, specifically the family of peroxiredoxins, i.e. thiol-specific antioxidant proteins possessing peroxidase activity, may be among the potential therapeutic agents. Peroxiredoxin VI (Prx VI), one of the agents belonging to this family, is capable of neutralizing organic and inorganic hydroperoxides, including peroxynitrites [9]. Moreover, several studies have already demonstrated a therapeutic effect of Prx VI, specifically its contribution to regeneration processes in the trachea epithelium after thermal [10, 11] and chemical burns [12]. Prx VI has been shown to make a beneficial effect on the healing of cut wounds [14]. Thus, peroxiredoxins may become prototypes of medicinal drugs possessing a potent antioxidant effect [13].