Research Article Early Effects of Hyperbaric Oxygen on Inducible Nitric Oxide Synthase Activity/Expression in Lymphocytes of Type 1 Diabetes Patients: A Prospective Pilot Study Ivana Resanovic , 1 Zoran Gluvic , 2 Bozidarka Zaric, 1 Emina Sudar-Milovanovic , 1 Aleksandra Jovanovic , 1 Davorka Milacic, 3 Radmilo Isakovic, 3 and Esma R. Isenovic 1 1 Institute of Nuclear Sciences Vinca, University of Belgrade, Laboratory of Radiobiology and Molecular Genetics, Belgrade, Serbia 2 Clinic for Internal Medicine, Zemun Clinical Hospital, School of Medicine, University of Belgrade, Belgrade, Serbia 3 Department of Hyperbaric Medicine, Zemun Clinical Hospital, Belgrade, Serbia Correspondence should be addressed to Ivana Resanovic; ivana_resanovic@yahoo.com and Esma R. Isenovic; isenovic@yahoo.com Received 11 May 2018; Revised 3 October 2018; Accepted 15 October 2018; Published 10 January 2019 Academic Editor: Maria L. Dufau Copyright © 2019 Ivana Resanovic et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This study aimed at examining the early effects of hyperbaric oxygen therapy (HBOT) on inducible nitric oxide synthase (iNOS) activity/expression in lymphocytes of type 1 diabetes mellitus (T1DM) patients. A group of 19 patients (mean age: 63 ± 2.1) with T1DM and with the peripheral arterial disease were included in this study. Patients were exposed to 10 sessions of HBOT in the duration of 1 h to 100% oxygen inhalation at 2.4 ATA. Blood samples were collected for the plasma C-reactive protein (CRP), plasma free fatty acid (FFA), serum nitrite/nitrate, and serum arginase activity measurements. Expression of iNOS and phosphorylation of p65 subunit of nuclear factor-κB (NFκB-p65), extracellular-regulated kinases 1/2 (ERK1/2), and protein kinase B (Akt) were examined in lymphocyte lysates by Western blot. After exposure to HBOT, plasma CRP and FFA were significantly decreased (p <0 001). Protein expression of iNOS and serum nitrite/nitrate levels were decreased (p <0 01), while serum arginase activity was increased (p <0 05) versus before exposure to HBOT. Increased phosphorylation of NFκB-p65 at Ser 536 (p <0 05) and decreased level of NFκB-p65 protein (p <0 001) in lymphocytes of T1DM patients were observed after HBOT. Decreased phosphorylation of ERK1/2 (p <0 05) and Akt (p <0 05) was detected after HBOT. Our results indicate that exposure to HBO decreased iNOS activity/expression via decreasing phosphorylation of ERK1/2 and Akt followed by decreased activity of NFκB. 1. Introduction Diabetes mellitus (DM) type 1 (T1DM) is a multifactorial autoimmune disease associated with significant morbidity and mortality related to microvascular and macrovascular complications [1, 2]. T1DM is associated with abnormal synthesis of nitric oxide (NO) via activation of inducible NO synthase (iNOS) [3, 4], and an increased level of iNOS enzyme is associated with DM-related vascular com- plications [5–8]. The iNOS gene expression is stimulated through activation of transcription factors, such as nuclear factor-κB (NFκB). Furthermore, induction of iNOS is mediated via stimulation of NFκB, by different stimuli including extracellular-regulated kinases (ERK1/2) and pro- tein kinase B (Akt) [9, 10]. Systemic hyperbaric oxygen (HBO) therapy (HBOT) has been proposed as a medical treatment for DM patients with the developed peripheral arterial disease. HBOT is defined as therapeutic inhalation of 100% oxygen in the elevated pressure controlled conditions, which induces micro- and macrovascular hemodynamic changes [11]. An increase in oxygen arterial partial pressure in hyperbaric conditions promotes better solubility of plasma oxygen. This further results in the preservation of vitality of tissues, reversibly damaged by atherosclerosis-induced ischemia, simulta- neously with microcirculation restoration [12]. Exposure Hindawi International Journal of Endocrinology Volume 2019, Article ID 2328505, 12 pages https://doi.org/10.1155/2019/2328505