N-acetyl cysteine improves the effects of corticosteroids in a mouse model of chlorine-induced acute lung injury
2015 (English)In: Toxicology, ISSN 0300-483X, E-ISSN 1879-3185, Vol. 328, 40-47 p.Article in journal (Refereed) Published
Chlorine (Cl-2) 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 1 h after Cl-2-exposure could improve protection against acute lung injury in Cl-2-exposed mice. BALB/c mice were exposed to 300 ppm Cl-2 during 15 min. Assessment of AHR and inflammatory cells in bronchoalveolar lavage was analyzed 24 h 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.
Place, publisher, year, edition, pages
2015. Vol. 328, 40-47 p.
Chlorine, Chemical-induced lung injury, Airway hyperresponsiveness, Respiratory mechanics, rticosteroids
Respiratory Medicine and Allergy
IdentifiersURN: urn:nbn:se:umu:diva-101406DOI: 10.1016/j.tox.2014.12.008ISI: 000349881500005PubMedID: 25497111OAI: oai:DiVA.org:umu-101406DiVA: diva2:839344