Maiellaro Marília, Correa-Costa Matheus, Vitoretti Luana Beatriz, Gimenes Júnior João Antônio, Câmara Niels Olsen Saraiva, Tavares-de-Lima Wothan, Farsky Sandra Helena Poliselli, Lino-dos-Santos-Franco Adriana
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Toxicol Appl Pharmacol. 2014 Aug 1;278(3):266-74. doi: 10.1016/j.taap.2014.05.003. Epub 2014 May 15.
Formaldehyde (FA) is an environmental and occupational pollutant, and its toxic effects on the immune system have been shown. Nevertheless, no data are available regarding the programming mechanisms after FA exposure and its repercussions for the immune systems of offspring. In this study, our objective was to investigate the effects of low-dose exposure of FA on pregnant rats and its repercussion for the development of allergic lung inflammation in offspring. Pregnant Wistar rats were assigned in 3 groups: P (rats exposed to FA (0.75 ppm, 1 h/day, 5 days/week, for 21 days)), C (rats exposed to vehicle of FA (distillated water)) and B (rats non-manipulated). After 30 days of age, the offspring was sensitised with ovalbumin (OVA)-alum and challenged with aerosolized OVA (1%, 15 min, 3 days). After 24 h the OVA challenge the parameters were evaluated. Our data showed that low-dose exposure to FA during pregnancy induced low birth weight and suppressed the development of allergic lung inflammation and tracheal hyperresponsiveness in offspring by mechanisms mediated by reduced anaphylactic antibodies synthesis, IL-6 and TNF-alpha secretion. Elevated levels of IL-10 were found. Any systemic alteration was detected in the exposed pregnant rats, although oxidative stress in the uterine environment was evident at the moment of the delivery based on elevated COX-1 expression and reduced cNOS and SOD-2 in the uterus. Therefore, we show the putative programming mechanisms induced by FA on the immune system for the first time and the mechanisms involved may be related to oxidative stress in the foetal microenvironment.
甲醛（FA）是一种环境和职业污染物，其对免疫系统的毒性作用已得到证实。然而，关于FA暴露后的编程机制及其对后代免疫系统的影响，目前尚无相关数据。在本研究中，我们的目的是探讨低剂量FA暴露对妊娠大鼠的影响及其对后代过敏性肺部炎症发展的影响。将妊娠Wistar大鼠分为3组：P组（暴露于FA的大鼠（0.75 ppm，每天1小时，每周5天，共21天））、C组（暴露于FA溶剂（蒸馏水）的大鼠）和B组（未处理的大鼠）。在30日龄后，用卵清蛋白（OVA）-明矾对后代进行致敏，并用雾化OVA（1%，15分钟，3天）进行激发。在OVA激发24小时后评估各项参数。我们的数据表明，孕期低剂量暴露于FA会导致出生体重降低，并通过减少过敏抗体合成、IL-6和TNF-α分泌介导的机制抑制后代过敏性肺部炎症和气管高反应性的发展。发现IL-10水平升高。在暴露的妊娠大鼠中未检测到任何全身改变，尽管基于子宫中COX-1表达升高以及cNOS和SOD-2降低，分娩时子宫环境中的氧化应激明显。因此，我们首次展示了FA对免疫系统诱导的假定编程机制，所涉及的机制可能与胎儿微环境中的氧化应激有关。
