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抗坏血酸治疗百草枯诱导肺纤维化的有益作用。

Beneficial effects of ascorbic acid to treat lung fibrosis induced by paraquat.

机构信息

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, Brazil.

出版信息

PLoS One. 2018 Nov 5;13(11):e0205535. doi: 10.1371/journal.pone.0205535. eCollection 2018.

Abstract

Paraquat (PQ) is one of the most widely employed herbicides that is used worldwide and it causes severe toxic effects in humans and animals. A PQ exposition can lead to pulmonary fibrosis (PF) and the mechanisms seem to be linked to oxidative stress, although other pathways have been suggested. Antioxidants can be useful as a therapy, although interventions with this kind of system are still controversial. Hence, this study has investigated the role of ascorbic acid (vitamin C) post-treatment on PQ-induced PF in male C57/BL6 mice. Pulmonary fibrosis was induced by a single PQ injection (10mg/kg; i.p.). The control group received a PQ vehicle. Seven days after the PQ or vehicle injections, the mice received vitamin C (150 mg/kg, ip, once a day) or the vehicle, over the following 7 days. Twenty-four hours after the last dose of vitamin C or the vehicle, the mice were euthanized and their bronchoalveolar lavage fluid (BALF) and their lungs were collected. The data obtained showed that vitamin C reduced the cellular recruitment, the secretion of IL-17 -a cytokine involved in neutrophils migration, TGF-β-a pro-fibrotic mediator and the collagen deposition. Moreover, vitamin C elevated the superoxide dismutase (SOD) and catalase levels, both antioxidant enzymes, but it did not alter the tracheal contractile response that was evoked by methacholine. Therefore, the researchers have highlighted the mechanisms of vitamin C as being non-invasive and have suggested it as a promising tool to treat lung fibrosis when it is induced by a PQ intoxication.

摘要

百草枯(PQ)是一种在全球范围内广泛使用的除草剂,对人类和动物有严重的毒性作用。PQ 暴露可导致肺纤维化(PF),其机制似乎与氧化应激有关,尽管也有其他途径被提出。抗氧化剂可用作治疗方法,尽管此类系统的干预措施仍存在争议。因此,本研究调查了 PQ 诱导的雄性 C57/BL6 小鼠 PF 后抗坏血酸(维生素 C)治疗的作用。通过单次 PQ 注射(10mg/kg;ip)诱导肺纤维化。对照组接受 PQ 载体。PQ 或载体注射后 7 天,小鼠接受维生素 C(150mg/kg,ip,每天一次)或载体,持续 7 天。最后一次给予维生素 C 或载体 24 小时后,处死小鼠,收集其支气管肺泡灌洗液(BALF)和肺。获得的数据表明,维生素 C 减少了细胞募集、白细胞介素 17(一种参与中性粒细胞迁移的细胞因子)的分泌、TGF-β-一种促纤维化介质和胶原蛋白沉积。此外,维生素 C 提高了超氧化物歧化酶(SOD)和过氧化氢酶的水平,这两种抗氧化酶,但它没有改变由乙酰甲胆碱引起的气管收缩反应。因此,研究人员强调了维生素 C 的作用机制是非侵入性的,并提出它作为一种有前途的工具,可用于治疗由 PQ 中毒引起的肺纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1669/6218022/3c1e651cd9aa/pone.0205535.g001.jpg

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