998 ISSN 0006-3509, Biophysics, 2017, Vol. 62, No. 6, pp. 998–1008. © Pleiades Publishing, Inc., 2017. Original Russian Text © M.G. Sharapov, A.E. Gordeeva, R.G. Goncharov, I.V. Tikhonova, V.K. Ravin, A.A. Temnov, E.E. Fesenko, V.I. Novoselov, 2017, published in Biofizika, 2017, Vol. 62, No. 6, pp. 1208–1220. The Effect of Exogenous Peroxiredoxin 6 on the State of Mesenteric Vessels and the Small Intestine in Ischemia–Reperfusion Injury M. G. Sharapov, A. E. Gordeeva, R. G. Goncharov, I. V. Tikhonova, V. K. Ravin, A. A. Temnov, E. E. Fesenko, and V. I. Novoselov* Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290 Russia *e-mail: novoselov-vi@rambler.ru Received July 14, 2017 Abstract⎯Oxidative stress is the main component of pathogenesis in ischemia–reperfusion injury. The administration of exogenous antioxidants suppresses oxidative stress and may decrease the severity of isch- emia–reperfusion injury. The intestine is one of the most sensitive organs to the effect of ischemia–reperfu- sion. A rat model of a small intestine ischemia–reperfusion injury, based on occlusion of the superior mes- enteric artery, was used in this work. Recombinant peroxiredoxin 6, a representative of an ancient family of peroxidases that are able to neutralize a broad range of both organic and inorganic peroxides, was used as an exogenous antioxidant. The intravenous administration of the exogenous peroxiredoxin 6 prior to ischemia– reperfusion minimizes tissue injury and reduces apoptotic cell death in the intestine and the mesenteric ves- sels. The impact of the exogenous peroxiredoxin 6 upon the NO level elevation in animal blood has been shown to be correlated with the enhanced inducible NO synthase expression. Thus, the use of exogenous per- oxiredoxin 6 in ischemia–reperfusion injury of the intestine and the mesenteric vessels promotes normaliza- tion of the tissue redox homeostasis, structure protection, and restoration of the microvasculature. Keywords: peroxiredoxin 6, ischemia–reperfusion, intestine, mesenteric vessels, gene expression DOI: 10.1134/S0006350917060239 INTRODUCTION A constant supply of oxygen and nutrients and withdrawal of products of metabolism is required to maintain the normal functional status of living tissue. If blood flow ceases (ischemia), metabolically active tissues are quickly damaged; upon reperfusion resto- ration of oxygen-rich blood flow and an avalanche- like formation of reactive oxygen species (ROS) occurs in the ischemic tissues, which causes damage to all biological macromolecules and the development of oxidative stress [1, 2]. It is now well known that isch- emia–reperfusion (I–R) injury is the main factor in the development of many pathological states [3]. The intestine is one of the most sensitive organs to the effect of ischemia–reperfusion [4]. Intestinal I–R injury is the cause of high mortality in patients with trauma or surgical procedures. The use of antioxidant drugs, which helps to neutralize the developed oxida- tive stress, is one of the possible approaches to the therapy of I–R injury; the use of antioxidant enzymes is the most promising method, since these, unlike low-molecular antioxidants, possess greater effi- ciency. Peroxiredoxins (Prx) among other members of an antioxidant enzyme family are of great interest, which, along with the ability to neutralize a wide spec- trum of ROS, have important chaperon and signal- regulatory features [5, 6]. Six peroxiredoxin types (Prx1–6) have been discovered in mammals, which are classified as 2-Cys-typical (Prx1–4), 2-Cys-atyp- ical (Prx5) and 1-Cys-peroxiredoxin (Prx6) depend- ing on the number of cysteine residues and the mech- anism of the peroxidase reaction. The level of perox- iredoxin was shown to increase with the development of pathologies accompanied by oxidative stress, con- tributing to the normalization of the ROS level in the affected tissues. In particular, a protective role of endogenous Prx6 has been shown during different pathologies of skin [7, 8], lung [9, 10], liver [11], kid- ney [12], eyes, and nervous system [13, 14]. A high level of therapeutic activity of exogenous Prx6 has been shown in our laboratory in various animal mod- els: total X-ray irradiation [15], chemical and thermal burns of the upper respiratory tract [16], and I–R inju- ries of the kidney [17] and colon [18]. In the present work, the protective action of exogenous Prx6 on rat mezenterial vessels and small intestine mucosa were studied in I–R injury and the possible mechanisms of this protection are discussed. Abbreviations: ROS, reactive oxygen species; I–R, ischemia– reperfusion; Prx, peroxiredoxin; LDF, laser Doppler flowmetry; PCR, polymerase chain reaction; RNS, reactive nitrogen spe- cies. BIOPHYSICS OF COMPLEX SYSTEMS