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臭氧暴露大鼠肺组织芳香烃羟化作用和脂质氧化状态的改变。

Alteration in aromatic hydroxylation and lipid oxidation status in the lungs of rats exposed to ozone.

机构信息

Environmental and Occupational Toxicology Division, Environmental Health Centre, Tunney's Pasture, Ottawa, Ontario, Canada.

出版信息

Toxicol Mech Methods. 2002;12(3):195-210. doi: 10.1080/15376520208951156.

Abstract

Fischer 344 rats were exposed to ozone by inhalation to identify sensitive indices of acute exposure. 5-Aminosalicylic acid (5-ASA) hydroxylation in bronchoalveolar lavage (BAL), an indicator of hydroxyl radical (*OH) formation, and lipid oxidation in various regions of airways, representing oxidative stress, were measured to verify whether they can function as markers of exposure. BAL cells and supernatants taken from rats that received saline or 5-ASA (ip, 50 mg/kg) prior to ozone exposure (0, 0.4, or 0.8 ppm for 4 h) were analyzed for products of lipid oxidation. *OH formation was assessed by analysis of the BAL supernatant for 5-aminotetrahydroxybenzoic acid (5-ATHBA), a hydroxylation product of 5-ASA. The tetrahydroxy derivative of 5-ASA was higher in the BAL of ozone-treated rats than in air controls, reaching significance (p <. 05) at 0.8 ppm of ozone, The products of lipid oxidation propanal and hexanal were higher in BAL cells taken from rats exposed to ozone, reaching significance (p <. 05) at a 0.8 ppm ozone level, compared to air control animals, irrespective of whether they received saline or 5-ASA prior to ozone exposure. Increases in cholesterol levels were also seen in BAL cells after rats were exposed to ozone. However, there were no significant dose-related changes in the lipid oxidation products in BAL supernatants after exposure to ozone. Lipid oxidation products in BAL cells and 5-ATHBA in lavage exhibited the potential to serve as markers of ozone exposure. This work was supported by Health Canada (#4320105) and Toxic Substances Research Initiatives (TSRI #60).

摘要

Fischer 344 大鼠通过吸入臭氧来识别急性暴露的敏感指标。测量支气管肺泡灌洗液(BAL)中 5-氨基水杨酸(5-ASA)羟化作用,这是羟基自由基(OH)形成的指标,以及气道各个区域的脂质氧化作用,代表氧化应激,以验证它们是否可以作为暴露的标志物。对接受生理盐水或 5-ASA(ip,50mg/kg)预处理后暴露于臭氧(0、0.4 或 0.8ppm,4 小时)的大鼠的 BAL 细胞和上清液进行分析,以检测脂质氧化产物。通过分析 BAL 上清液中的 5-氨基四羟基苯甲酸(5-ATHBA)来评估OH 形成,这是 5-ASA 的羟化产物。与空气对照组相比,臭氧处理大鼠的 BAL 中 5-ASA 的四羟基衍生物更高,在 0.8ppm 的臭氧水平下达到显著水平(p<0.05)。与空气对照组相比,暴露于臭氧的大鼠的 BAL 细胞中丙醛和己醛的脂质氧化产物更高,在 0.8ppm 臭氧水平下达到显著水平(p<0.05),无论它们是否在暴露于臭氧之前接受了生理盐水或 5-ASA。暴露于臭氧后,BAL 细胞中的胆固醇水平也有所增加。然而,暴露于臭氧后,BAL 上清液中的脂质氧化产物没有明显的剂量相关变化。BAL 细胞中的脂质氧化产物和灌洗液中的 5-ATHBA 具有作为臭氧暴露标志物的潜力。这项工作得到了加拿大卫生部(#4320105)和有毒物质研究倡议(TSRI#60)的支持。

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