Environmental Toxicology and Pharmacology 45 (2016) 187–192 Contents lists available at ScienceDirect Environmental Toxicology and Pharmacology journal homepage: www.elsevier.com/locate/etap Sulfur mustard causes oxidants/antioxidants imbalance through the overexpression of free radical producing-related genes in human mustard lungs Eisa Tahmasbpour Marzony, Amir Nejad-Moghadam, Mostafa Ghanei, Yunes Panahi ∗ Chemical Injuries Research Center, Baqiatallah University of Medical Sciences, Tehran, Iran a r t i c l e i n f o Article history: Received 31 March 2016 Received in revised form 31 May 2016 Accepted 2 June 2016 Available online 3 June 2016 Keywords: Lung tissue Oxidative stress Oxidants/antioxidants imbalance ROS producing-related genes Sulfur mustard a b s t r a c t The aim of this study is to analyze oxidative stress (OS) and changes in expression of reactive oxygen species (ROS) producing-related genes in mustard lungs. Human lung biopsies provided from con- trols (n = 5) and sulfur mustard (SM)-exposed patients (n = 6). Changes in expression of dual oxidases (DUOXs), aldehyde oxidase 1 (AOX1), thyroid peroxidase (TPO), myeloperoxidase (MPO) and eosinophil Peroxidase (EPO) were measured using RT 2 Profiler TM PCR Array. OS was evaluated by determining bron- choalveolar lavage fluids (BALF) levels of total antioxidant capacity (TAC) and malondialdehyde (MDA). Higher TAC value was observed in BALF of controls compared with patients (0.138 ± 0.02683 mol/l vs 0.0942 ± 0.01793 mol/l), whereas a significant increase in MDA concentration was found in patients (0.486 ± 0.04615 nmol/l vs 0.6467 ± 0.05922 nmol/l). All ROS producing-related genes were overex- pressed in the order AOX1> MPO> DUOX2> DUOX1> TPO> EPO. Upregulation of these genes may be a reason for overproduction of ROS, oxidants/antioxidants imbalance, OS and respiratory failures in mustard lungs. © 2016 Published by Elsevier B.V. 1. Introduction 2,2 ′ -Dichlorodiethyl sulfide, commonly known as sulfur mus- tard (SM), is an oily lipophilic liquid which has been used as a chemical warfare agent. It is one of the major chemical warfare agents developed and used during World War I (Ghabili et al., 2011; Tahmasbpour et al., 2015). But the highest unconventional appli- cation of SM occurred in Iran-Iraq war (1980–1988). During that period, it injured more than hundred thousand Iranians, which one-third of them are still suffering from late effects (Kehe and Szinicz, 2005; Namazi et al., 2009; Tahmasbpour et al., 2016a). Respiratory system is the primary target for SM toxicity following inhalation exposure (Ghanei and Harandi 2007). Recently studies have shown that exposure to SM is the leading cause of persis- tent lung disease, progressive deterioration in lung function and mortality (Ghanei and Harandi 2010). Recent investigations have also revealed several long-term pulmonary complications such as chronic bronchitis, asthma, bronchiectasis, large airway narrow- ing, pulmonary fibrosis, as well as more obstructive spirometric ∗ Corresponding author at: Chemical Injuries Research Center, Baqiatallah Uni- versity of Medical Sciences, P.O. Box 19945-581, Tehran, Iran. E-mail addresses: tahmasb@hotmail.com (E. Tahmasbpour Marzony), yunespanahi@yahoo.com (Y. Panahi). and chronic obstructive pulmonary disease (COPD) among exposed patients (Balali-Mood et al., 2008; Shohrati et al., 2008). Neverthe- less, the exact cellular and molecular mechanisms of SM toxicity on lungs are still unclear, hence there is no effective treatment to prevent further pulmonary injury or induce repair. Furthermore, current medications are mainly effective for improving symptoms and exacerbations but generally do not slow down progression of the disease. As a result, a better understanding of underlying molec- ular mechanisms of SM toxicity on lungs is crucial for creating more developed diagnostic and therapeutic approach. One of these mechanisms is likely related to increased oxidative stress (OS) induced by reactive oxidative species (ROS). Overex- pression of some ROS producing-related enzymes with oxidase and peroxidase activities, especially aldehyde oxidase-1 (AOX1), dual oxidases (DUOX1 and DUOX2), myeloperoxidase (MPO), eosinophil peroxidase (EPO) and thyroid peroxidase (TPO) are the hypoth- esized events which may be contributed in ROS production and lung injury among SM-exposed patients. Dual oxidases are more prone to direct ROS (H 2 O 2 ) production than peroxidase activity (Tahmasbpour et al., 2015). Therefore, identification of altered com- ponents of this complex system could provide important insights into the biological basis of increased oxidative stress in mustard lung and potential targets of clinical intervention. To the best of our knowledge, there is no report of these genes expression in lung tissue of SM exposed patients. As part of ongoing research into the http://dx.doi.org/10.1016/j.etap.2016.06.001 1382-6689/© 2016 Published by Elsevier B.V.