Issa Layali1, Alireza Shahriary2, Nima Rahmani Talatappe2, Eisa Tahmasbpour3, Hossein Rostami4, Asghar Beigi Harchegani2. 1. a Department of Biochemistry , Sari Branch, Islamic Azad University , Sari , Iran. 2. b Chemical Injuries Research Center, System Biology and Poisonings Institute , Baqiyatallah University of Medical Sciences , Tehran , Iran. 3. c Laboratory of Regenerative Medicine & Biomedical Innovations , Pasteur Institute of Iran , Tehran , Iran. 4. d Heltch Research Center, Life Style Institute , Baqiyatallah University of Medical Sciences , Tehran , Iran.
Abstract
CONTEXT: Sulfur mustard (SM) is a lipophilic and reactive chemical compound that targets human airway system. OBJECTIVE: Glutathione (GSH) depletion, oxidative stress (OS) status, and changes in expression of GSH-dependent antioxidant enzymes were considered in human mustard lungs. MATERIALS AND METHODS: Lung biopsies and bronchoalveolar lavage (BAL) were collected from non-exposed (n = 10) individuals and SM-exposed patients (n = 12). Alterations in expression of GSH-dependent enzymes were studied using RT2 Profiler™ PCR array. OS was evaluated by determining BAL fluid levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and GSH. RESULTS: Mean TAC (0.142 ± 0.027 µmol/l) and GSH (4.98 ± 1.02 nmol/l) in BAL fluids of control group was significantly higher (p < .05) than those in SM-exposed patients (TAC = 0.095 ± 0.018 µmol/l and GSH= 3.09 ± 1.02 nmol/l), while MDA level in BAL fluids of these patients (0.71 ± 0.06 nmol/l) was significantly (p = .001) higher than that in controls (0.49 ± 0.048 nmol/l). Glutathione peroxidases (GPXs), glutathione-s-transferases (GSTs), and glutathione synthetase (GSS) enzymes were overexpressed in mustard lung biopsies, while glutathione reductase (GSR) was significantly downregulated (14.95-fold). CONCLUSIONS: GSH depletion induced by GSR downregulation may be a major mechanism of SM toxicity on human lung. Despite overexpression of GSTs and GPXs genes, GSH depletion may decline the productivity of these enzymes and total antioxidants capacity, which is associated with OS.
CONTEXT: Sulfur mustard (SM) is a lipophilic and reactive chemical compound that targets human airway system. OBJECTIVE:Glutathione (GSH) depletion, oxidative stress (OS) status, and changes in expression of GSH-dependent antioxidant enzymes were considered in human mustard lungs. MATERIALS AND METHODS: Lung biopsies and bronchoalveolar lavage (BAL) were collected from non-exposed (n = 10) individuals and SM-exposed patients (n = 12). Alterations in expression of GSH-dependent enzymes were studied using RT2 Profiler™ PCR array. OS was evaluated by determining BAL fluid levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and GSH. RESULTS: Mean TAC (0.142 ± 0.027 µmol/l) and GSH (4.98 ± 1.02 nmol/l) in BAL fluids of control group was significantly higher (p < .05) than those in SM-exposed patients (TAC = 0.095 ± 0.018 µmol/l and GSH= 3.09 ± 1.02 nmol/l), while MDA level in BAL fluids of these patients (0.71 ± 0.06 nmol/l) was significantly (p = .001) higher than that in controls (0.49 ± 0.048 nmol/l). Glutathione peroxidases (GPXs), glutathione-s-transferases (GSTs), and glutathione synthetase (GSS) enzymes were overexpressed in mustard lung biopsies, while glutathione reductase (GSR) was significantly downregulated (14.95-fold). CONCLUSIONS:GSH depletion induced by GSR downregulation may be a major mechanism of SMtoxicity on human lung. Despite overexpression of GSTs and GPXs genes, GSH depletion may decline the productivity of these enzymes and total antioxidants capacity, which is associated with OS.
Authors: Ratnakar Tripathi; Praveen K Balne; Nishant R Sinha; Lynn M Martin; Sabeeh Kamil; James R Landreneau; Suneel Gupta; Jason T Rodier; Prashant R Sinha; Nathan P Hesemann; Alexandria C Hofmann; Michael K Fink; Shyam S Chaurasia; Rajiv R Mohan Journal: Transl Vis Sci Technol Date: 2020-11-02 Impact factor: 3.283