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苯并(a)芘诱导的大鼠肺部炎症、水肿、表面活性剂功能障碍及损伤:法尼醇的缓解作用

Benzo(a)pyrene-induced pulmonary inflammation, edema, surfactant dysfunction, and injuries in rats: alleviation by farnesol.

作者信息

Qamar Wajhul, Khan Abdul Quaiyoom, Khan Rehan, Lateef Abdul, Tahir Mir, Rehman Muneeb U, Ali Farrah, Sultana Sarwat

机构信息

Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Jamia Hamdard, Hamdard University, Hamdard Nagar, New Delhi, India.

出版信息

Exp Lung Res. 2012 Feb;38(1):19-27. doi: 10.3109/01902148.2011.632064. Epub 2011 Dec 14.

DOI:10.3109/01902148.2011.632064
PMID:22168545
Abstract

Benzo(a)pyrene (B(a)P) is a well-known environmental contaminant and carcinogen. Its sources include tobacco smoke, automobile exhaust, forest fire, and other combustion processes. Farnesol, an active principle of Vachellia farnesiana and other aromatic plants, possesses preventive properties against various toxicities. Present study was designed to estimate chemopreventive effects of farnesol against B(a)P-induced pulmonary injuries. To determine the protective effects of farnesol, it was administered orally at 2 doses (100 and 200 mg/kg body weight [b.w.]) once daily for 14 days. Rats were exposed intratracheally to B(a)P, 5 mg/kg b.w. on days 12 and 14, thereafter assessed for pulmonary toxicities 24 hours post last dose of B(a)P. B(a)P-induced edema, inflammation, oxidative stress, and consequent damages in lungs were assessed in terms of total protein, total cell count, nitric oxide (NO), lactate dehydrogenase (LDH), alkaline phosphatase, and in bronchoalveolar lavage fluid (BALF). B(a)P also reduced the levels of phospholipids (lung surfactants) in BALF. However, pretreatment with farnesol at both the doses significantly reduced the lung injuries and inflammatory responses. Farnesol also protected the levels of phospholipids to normal when compared with control. It also modified the activities of B(a)P metabolizing enzymes NADPH-cytochrome P450 reductase, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) in lung tissue of rats. Present findings suggest a prominent role of farnesol against B(a)P-induced lung inflammation, edema, surfactant dysfunction, and epithelial damages in Wistar rats. In conclusion, farnesol shows lung protection against B(a)P toxicities in Wistar rats.

摘要

苯并(a)芘(B(a)P)是一种著名的环境污染物和致癌物。其来源包括烟草烟雾、汽车尾气、森林火灾及其他燃烧过程。法尼醇是法氏金合欢和其他芳香植物的一种活性成分,具有预防多种毒性的特性。本研究旨在评估法尼醇对B(a)P诱导的肺损伤的化学预防作用。为确定法尼醇的保护作用,将其以两种剂量(100和200毫克/千克体重[b.w.])每日口服一次,持续14天。在第12天和第14天,大鼠经气管内给予5毫克/千克体重的B(a)P,之后在最后一剂B(a)P给药24小时后评估肺毒性。通过支气管肺泡灌洗液(BALF)中的总蛋白、总细胞计数、一氧化氮(NO)、乳酸脱氢酶(LDH)、碱性磷酸酶评估B(a)P诱导的水肿、炎症、氧化应激及随之而来的肺损伤。B(a)P还降低了BALF中磷脂(肺表面活性剂)的水平。然而,两种剂量的法尼醇预处理均显著减轻了肺损伤和炎症反应。与对照组相比,法尼醇还将磷脂水平维持在正常水平。它还改变了大鼠肺组织中B(a)P代谢酶NADPH-细胞色素P450还原酶、微粒体环氧化物水解酶(mEH)和谷胱甘肽S-转移酶(GST)的活性。目前的研究结果表明,法尼醇在Wistar大鼠中对B(a)P诱导的肺部炎症、水肿、表面活性剂功能障碍和上皮损伤具有显著作用。总之,法尼醇对Wistar大鼠的B(a)P毒性具有肺保护作用。

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