Schapochnik Adriana, da Silva Marcia Rodrigues, Leal Mayara Peres, Esteves Janete, Hebeda Cristina Bichels, Sandri Silvana, de Fátima Teixeira da Silva Daniela, Farsky Sandra Helena Poliseli, Marcos Rodrigo Labat, Lino-Dos-Santos-Franco Adriana
Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), São Paulo, Brazil.
Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
Toxicol Appl Pharmacol. 2018 Sep 15;355:60-67. doi: 10.1016/j.taap.2018.06.020. Epub 2018 Jun 23.
A high incidence of intentional or accidental paraquat (PQ) ingestion is related to irreversible lung fibrosis and no effective therapy is currently available. Vitamin D has emerged with promising results as an immunomodulatory molecule when abrogating the inflammatory responses of lung diseases. Therefore, we have investigated the role of vitamin D treatments on PQ-induced lung fibrosis in male C57/BL6 mice. Lung fibrosis was induced by a single injection of PQ (10 mg/kg; i.p.). The control group received PQ vehicle. Seven days later, after the PQ injection or the vehicle injection, the mice received vitamin D (5 μg/kg, i.p., once a day) or vehicle, for a further 7 days. Twenty-four hours after the last dose of vitamin D or the vehicle, the analysis were performed. The vitamin D treatments reduced the number of leukocytes in their BALF and they decreased the IL-6, IL-17, TGF-beta and MMP-9 levels and the abrogated collagenase deposits in their lung tissues. Conversely, the vitamin D treatments increased the resolvin D levels in their BALF. Moreover, their tracheal contractility was also significantly reduced by the vitamin D treatments. Altogether, the data that was obtained showed a promising use of vitamin D, in treating the lung fibrosis that had been induced by the PQ intoxications. This may improve its prognostic use for a non-invasive and low cost therapy.
故意或意外摄入百草枯（PQ）的发生率很高，这与不可逆的肺纤维化有关，目前尚无有效的治疗方法。维生素D作为一种免疫调节分子，在消除肺部疾病的炎症反应方面已显示出有前景的结果。因此，我们研究了维生素D治疗对雄性C57/BL6小鼠PQ诱导的肺纤维化的作用。通过单次注射PQ（10 mg/kg；腹腔注射）诱导肺纤维化。对照组接受PQ溶媒。7天后，在注射PQ或溶媒后，小鼠接受维生素D（5 μg/kg，腹腔注射，每天一次）或溶媒，持续7天。在最后一剂维生素D或溶媒注射24小时后进行分析。维生素D治疗减少了其支气管肺泡灌洗液（BALF）中的白细胞数量，并降低了其肺组织中白细胞介素-6（IL-6）、白细胞介素-17、转化生长因子-β（TGF-β）和基质金属蛋白酶-9（MMP-9）的水平，以及消除了胶原酶沉积。相反，维生素D治疗增加了其BALF中消退素D的水平。此外，维生素D治疗还显著降低了它们的气管收缩性。总之，所获得的数据表明维生素D在治疗PQ中毒诱导的肺纤维化方面有前景。这可能会改善其在非侵入性和低成本治疗中的预后应用。
