Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
Department of Biomedical, Dental and Morphological and Functional Imaging University of Messina, Messina, Italy.
Cell Physiol Biochem. 2021 Nov 18;55(6):704-725. doi: 10.33594/000000471.
BACKGROUND/AIMS: Pulmonary fibrosis can be caused by genetic abnormalities, autoimmune disorders or exposure to environmental pollutants. All these causes have in common the excessive production of oxidative stress species that initiate a cascade of molecular mechanism underlying fibrosis in a variety of organs, including lungs. The chemical name of Atrazine (ATR) is 6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine, and it is the most commonly used broad-spectrum herbicide in agricultural crops. Additionally, Bleomycin is a chemotherapeutic agent often used for different lymphoma with a seriously pulmonary complication. The most accredited hypothesis that may explain the mechanism of toxicity induced by ATR or bleomycin is exactly the production of reactive oxygen species (ROS) that leads to an unbalance in the physiological anti-oxidant system. However, until today, nobody has investigated the effect of ATR exposure during pulmonary fibrosis.
Mice were subject to ATR exposure, to bleomycin injection or to both. At the end of experiment, the lungs and blood were collected. Additionally, we analyzed by different test such as open field, pole and rotarod test or other we investigated the effects of ATR or bleomycin exposure on behavior.
Following ATR or bleomycin induction, we found a significant increase in lung damage, fibrosis, and oxidative stress. This condition was significantly worsened when the animals injected with bleomycin were also exposed to ATR. Additionally, we observed significant motor and non-motor impairment in animals exposed to ATR.
Our study demonstrates that ATR exposure, decrease nuclear factor-erythroid 2-related factor (Nrf2) pathways in both lung and brain.
背景/目的：肺纤维化可由遗传异常、自身免疫性疾病或暴露于环境污染物引起。所有这些原因的共同点是活性氧（ROS）的过度产生，引发了一系列分子机制，导致包括肺部在内的多种器官发生纤维化。阿特拉津（ATR）的化学名称为 6-氯-N-乙基-N'-(1-甲基乙基）-1,3,5-三嗪-2,4-二胺，是农业作物中最常用的广谱除草剂。此外，博莱霉素是一种化疗药物，常用于治疗不同的淋巴瘤，伴有严重的肺部并发症。可以解释 ATR 或博莱霉素诱导毒性机制的最被认可的假设是活性氧（ROS）的产生，导致生理抗氧化系统失衡。然而，直到今天，还没有人研究过 ATR 暴露在肺纤维化中的作用。
将小鼠暴露于 ATR 下，注射博莱霉素或两者兼有。实验结束时，收集肺部和血液。此外，我们通过不同的测试（如旷场、杆和转棒测试）进行分析，或进行其他测试，研究 ATR 或博莱霉素暴露对行为的影响。
ATR 或博莱霉素诱导后，我们发现肺部损伤、纤维化和氧化应激显著增加。当注射博莱霉素的动物同时暴露于 ATR 时，这种情况明显恶化。此外，我们还观察到暴露于 ATR 的动物出现了明显的运动和非运动障碍。
我们的研究表明，ATR 暴露会降低肺和脑中的核因子-红细胞 2 相关因子（Nrf2）途径。
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