title: N-acetyl cysteine improves the effects of corticosteroids in a mouse model of chlorine-induced acute lung injury.
abstract: Chlorine (Cl2) causes tissue damage and a neutrophilic inflammatory response in the airways manifested by pronounced airway hyperreactivity (AHR). The importance of early anti-inflammatory treatment has previously been addressed. In the previous study, both high-dose and low-dose of dexamethasone (DEX) decreased the risk of developing delayed effects, such as persistent lung injuries, while only high-dose treatment could significantly counteract acute-phase effects. One aim of this study was to evaluate whether a low-dose of DEX in combination with the antioxidant N-acetyl cysteine (NAC) and if different treatments (Triptolide, Reparixin and Rolipram) administered 1h after Cl2-exposure could improve protection against acute lung injury in Cl2-exposed mice. BALB/c mice were exposed to 300 ppm Cl2 during 15 min. Assessment of AHR and inflammatory cells in bronchoalveolar lavage was analyzed 24h post exposure. Neither of DEX nor NAC reduced the AHR and displayed only minor effects on inflammatory cell influx when given as separate treatments. When given in combination, a protective effect on AHR and a significant reduction in inflammatory cells (neutrophils) was observed. Neither of triptolide, Reparixin nor Rolipram had an effect on AHR but Triptolide had major effect on the inflammatory cell influx. Treatments did not reduce the concentration of either fibrinogen or plasminogen activator inhibitor-1 in serum, thereby supporting the theory that the inflammatory response is not solely limited to the lung. These results provide a foundation for future studies aimed at identifying new concepts for treatment of chemical-induced lung injury. Studies addressing combination of anti-inflammatory and antioxidant treatment are highly motivated.
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Wigenstam
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Koch
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden; Department of Public Health and Clinical Medicine, Division of Respiratory Medicine, Umeå University, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bucht
authors.affiliation: Swedish Defence Research Agency, Division of CBRN Defence and Security, Umeå, Sweden. Electronic address: sofia.jonasson@foi.se.
authors.forename: Sofia
authors.initials: S
authors.lastname: Jonasson
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002713:Chlorine; D019610:Cytoprotection; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005740:Gases; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013997:Time Factors
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D005740:Gases; D017395:Plasminogen Activator Inhibitor 1; D002713:Chlorine; D003907:Dexamethasone; D005340:Fibrinogen; D000111:Acetylcysteine
keywords: Airway hyperresponsiveness; Chemical-induced lung injury; Chlorine; Corticosteroids; Respiratory mechanics