Silva Ibrahim Beatriz, Miranda da Silva Cristiane, Barioni Éric Diego, Correa-Costa Matheus, Drewes Carine Cristiane, Saraiva Câmara Niels Olsen, Tavares-de-Lima Wothan, Poliselli Farsky Sandra Helena, Lino-dos-Santos-Franco Adriana
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil.
Toxicol Lett. 2015 Jun 1;235(2):147-54. doi: 10.1016/j.toxlet.2015.04.001. Epub 2015 Apr 3.
Formaldehyde (FA) is an environmental and occupational pollutant that induces programming mechanisms on the acquired immune host defense in offspring when exposed during the prenatal period. Hence, here we investigated whether the exposure of FA on pregnant rats could affect the development of an innate acute lung injury in offspring induced by lipopolissacaride (LPS) injection. Pregnant Wistar rats were exposed to FA (0.92 mg/m(3)) or vehicle (distillated water), both 1 h/day, 5 days/week, from 1 to 21 days of pregnancy. Non-manipulated rats were used as control. After 30 days of birth, the offspring was submitted to injection of LPS (Salmonella abortus equi, 5 mg/kg, i.p.). Systemic and lung inflammatory parameters were evaluated 24 h later. Exposure to FA during gestation abolished the development of acute lung injury in offspring, as observed by reduced number of leukocytes in the bronchoalveolar fluid (BAL), in the blood and in the bone marrow, and decreased myeloperoxidase activity in the lung. Moreover, phagocytes from BAL presented normal phagocytosis, but reduced oxidative burst. Alterations on the profile of inflammatory cytokines were evidenced by reduced mRNA levels of IL-6 and elevated levels of IL-10 and IFN gamma in the lung tissue. Indeed, mRNA levels of toll-likereceptor-4 and nuclear factor-kappa B translocation into the nucleus were also reduced. Additionally, hyperresponsiveness to methacholine was blunted in the trachea of offspring of FA exposed mothers. Together, our data clearly show that FA exposure in the prenatal period modifies the programming mechanisms of the innate defense in the offspring leading to impaired defense against infections.
甲醛（FA）是一种环境和职业污染物，在孕期接触时会对后代获得性免疫宿主防御系统产生编程机制。因此，我们在此研究了孕期给孕鼠暴露于FA是否会影响脂多糖（LPS）注射诱导的后代先天性急性肺损伤的发展。将怀孕的Wistar大鼠从妊娠第1天至21天每天1小时、每周5天暴露于FA（0.92毫克/立方米）或溶剂（蒸馏水）。未进行处理的大鼠用作对照。出生30天后，给后代注射LPS（马流产沙门氏菌，5毫克/千克，腹腔注射）。24小时后评估全身和肺部炎症参数。孕期暴露于FA可消除后代急性肺损伤的发展，这可通过支气管肺泡灌洗液（BAL）、血液和骨髓中白细胞数量减少以及肺中髓过氧化物酶活性降低来观察到。此外，BAL中的吞噬细胞呈现正常吞噬作用，但氧化爆发减少。肺组织中IL-6的mRNA水平降低以及IL-10和IFNγ水平升高证明了炎症细胞因子谱的改变。确实，Toll样受体-4的mRNA水平以及核因子-κB向细胞核的转位也降低了。此外，暴露于FA的母亲的后代气管对乙酰甲胆碱的高反应性减弱。总之，我们的数据清楚地表明，孕期暴露于FA会改变后代先天性防御的编程机制，导致抗感染防御受损。
