Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin
Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin
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DOI：
10.1093/toxres/tfaa079
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发表时间：
2020-12-01
影响因子：
2.1
通讯作者：
Brucker, Natalia
中科院分区：
文献类型：
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作者：
Bernardini, Leticia;Barbosa, Eduardo;Brucker, Natalia
甲醛（FA）暴露已被证明会增加哮喘和癌症的风险。本研究旨在评估FA吸入28天对小鼠氧化应激、炎症过程、遗传毒性和整体DNA甲基化的影响，以及研究褪黑激素的潜在保护作用。为此，对肺、肝和肾组织、血液和骨髓进行了分析。采用支气管肺泡灌洗法测定炎症指标。测定脂质过氧化（TBARS）、蛋白质羰基（PCO）、非蛋白质硫醇（NPSH）、过氧化氢酶活性（CAT）、彗星试验、微核（MN）和整体甲基化。暴露于5-ppm FA导致肺氧化损伤，呈现TBARS和NO水平显著增加和NPSH水平降低，除了增加用于支气管肺泡灌洗的炎性细胞。同样，在肝组织中，暴露于5 ppm FA增加了TBARS和PCO水平，降低了NPSH水平。此外，FA显著诱导DNA损伤，表现为%尾矩和MN频率的增加。应用褪黑激素对暴露于FA的小鼠进行预处理，改善了肺和肝组织中的炎症和氧化损伤，并减弱了骨髓细胞中MN的形成。肺组织学研究加强了在生化参数中观察到的结果，证明了褪黑激素的潜在有益作用。因此，我们的研究结果表明，FA暴露与重复剂量可能会诱导氧化损伤，炎症和遗传毒性作用，褪黑激素最大限度地减少了小鼠吸入FA引起的毒性作用。
Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.