RESUMO
High-level concentrations of chlorine (Cl2) can cause life-threatening lung injuries and the objective in this study was to understand the pathogenesis of short-term sequelae of Cl2-induced lung injury and to evaluate whether pre-treatment with the antioxidant N-acetyl cysteine (NAC) could counteract these injuries using Cl2-exposed precision-cut lung slices (PCLS). The lungs of Sprague-Dawley rats were filled with agarose solution and cut into 250 µm-thick slices that were exposed to Cl2 (20-600 ppm) and incubated for 30 min. The tissue slices were pre-treated with NAC (5-25 mM) before exposure to Cl2. Toxicological responses were analyzed after 5 h by measurement of LDH, WST-1 and inflammatory mediators (IL-1ß, IL-6 and CINC-1) in medium or lung tissue homogenate. Exposure to Cl2 induced a concentration-dependent cytotoxicity (LDH/WST-1) and IL-1ß release in medium. Similar cytokine response was detected in tissue homogenate. Contraction of larger airways was measured using electric-field-stimulation method, 200 ppm and control slices had similar contraction level (39 ± 5%) but in the 400 ppm Cl2 group, the evoked contraction was smaller (7 ± 3%) possibly due to tissue damage. NAC-treatment improved cell viability and reduced tissue damage and the contraction was similar to control levels (50 ± 11%) in the NAC treated Cl2-exposed slices. In conclusion, Cl2 induced a concentration-dependent lung tissue damage that was effectively prevented with pre-treatment with NAC. There is a great need to improve the medical treatment of acute lung injury and this PCLS method offers a way to identify and to test new concepts of treatment of Cl2-induced lung injuries.
Assuntos
Acetilcisteína/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cloro/toxicidade , Mediadores da Inflamação/metabolismo , Lesão Pulmonar/prevenção & controle , Pulmão/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/metabolismo , Citoproteção , Relação Dose-Resposta a Droga , Feminino , Técnicas In Vitro , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Ratos Sprague-DawleyRESUMO
Numerous studies demonstrated that the use of lead (Pb)-containing ammunition is associated with mainly chronic health problems and also is a burden on the environment and wildlife. Recently, a number of reports showed evidence of undesirable acute health effects related to the use of newly developed Pb-free small-caliber ammunition. In this study, particles from leaded and Pb-free ammunition were collected in liquid collection medium, in a highly controlled chamber, while firing a pistol (9 mm) or a rifle (7.62 × 51 mm). The emitted particles were typically smaller than 4 µm, with the great majority in even smaller size ranges, as shown by gravimetrical analysis and a multistage impactor. Chemical analysis revealed significant differences in content and concentration of several metals in the particles. After administration of the liquids to alveolar and bronchial in vitro cell systems, particles were taken up by the cells; the Pb-free particles displayed higher cytotoxicity (EC50 = 2 µg/cm(2)) than particles from Pb ammunition. High correlation factors (>0.9) were found between cell death and content of copper and zinc. Particles from both Pb-containing and Pb-free ammunition were able to induce oxidative stress and the proinflammatory marker interleukin (IL)-8 in both in vitro systems. These results support previous findings that indicate an association between gunshot emissions and metal fume fever. This study demonstrates the usefulness of combining chemical data with biological in vitro responses in assessing acute toxicological effects from emissions from firing both Pb and Pb-free ammunition.
Assuntos
Brônquios/efeitos dos fármacos , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Armas de Fogo , Material Particulado/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Células Cultivadas , Humanos , Tamanho da Partícula , Alvéolos PulmonaresRESUMO
The main objective of this study was to perform an initial characterization of Swedish soldiers' exposure to air pollutants in Afghanistan and screen for potential health hazards. Stationary monitoring was performed in two military camps, International Security Assistance Force Headquarters in Kabul and Camp Northern Lights in Mazar-e Sharif, at both outdoor and indoor locations. A broad screening including particulate matter (PM10 and PM2.5), polycyclic aromatic hydrocarbons (PAHs), oxygenated PAHs, n-alkanes, nitrogen dioxide (NO2), sulfur dioxide, toxic metals, and volatile organic compounds (VOCs) was performed over 2 weeks in the autumn of 2009. The results were compared to current air quality guidelines. Particulate matter was identified as the main potential health hazard since military exposure guidelines for marginal effects were exceeded outdoors. In addition, especially in Kabul, levels of particle-bound PAHs and oxy-PAHs were high, whereas levels of toxic metals were generally low. Among gaseous pollutants, elevated NO2 levels in Kabul supported combustion as a major contributor to the poor air quality. VOC levels were generally low, but levels of some pollutants exceeded current guidelines. Because of elevated concentrations of particles with a high content of toxic organics, further monitoring and characterization of the occupational environment are warranted.