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全氟辛酸经口暴露21天后对小鼠肝脏的毒性作用。

Perfluorooctanoic acid-induced hepatic toxicity following 21-day oral exposure in mice.

作者信息

Son Hee-Young, Kim Sang-Hyun, Shin Hong-In, Bae Han Ik, Yang Jae-Ho

机构信息

Department of Pharmacology, Kyungpook National University Medical School, Daegu, Republic of Korea.

出版信息

Arch Toxicol. 2008 Apr;82(4):239-46. doi: 10.1007/s00204-007-0246-x. Epub 2007 Sep 14.

Abstract

Perfluorooctanoic acid (PFOA) is a member of the perfluoroalkyl acids that have wide commercial applications and is a widespread pollutant of toxicological importance that has been detected in environmental matrices. The NOAEL and LOAEL of PFOA in rodent were reported 1 and 10 ppm, respectively. The current study characterizes the hepatic toxicities of PFOA in mice. Male ICR mice were exposed continuously to 0, 2, 10, 50 and 250 ppm of PFOA in drinking water for 21 days. Food and water consumption decreased in mice exposed to 250 ppm of PFOA. Mean body weight gain was reduced in mice exposed to 50 and 250 ppm of PFOA. The size and relative weight of the liver increased dose-dependently in PFOA-treated mice. Serum enzyme activities, alanine aminotransferase and aspartate aminotransferase, increased in mice exposed to PFOA in a dose-dependent manner. In the histopathological evaluation, the liver of PFOA-treated mice showed remarkable hepatocytomegaly and acidophilic cytoplasm. At the high doses of PFOA, diffuse hepatic damage by multifocal coagualation and liquefaction necrosis were noted. In contrast to the remarkable change of liver, the kidney had little change. The size and relative weights of the kidney, biomarkers of kidney damage (blood urea nitrogen, creatinine), and histopathological changes had no differences between PFOA-untreated and PFOA-treated mice. In conclusion, our results demonstrate that PFOA causes a toxic effect on the liver but not to the kidney.

摘要

全氟辛酸(PFOA)是具有广泛商业应用的全氟烷基酸的一种,是一种在环境基质中已被检测到的具有毒理学重要性的广泛污染物。据报道,PFOA在啮齿动物中的无观察到有害作用水平(NOAEL)和最低观察到有害作用水平(LOAEL)分别为1 ppm和10 ppm。本研究描述了PFOA对小鼠的肝脏毒性。雄性ICR小鼠连续21天饮用含0、2、10、50和250 ppm PFOA的水。暴露于250 ppm PFOA的小鼠食物和水消耗量减少。暴露于50和250 ppm PFOA的小鼠平均体重增加减少。PFOA处理的小鼠肝脏大小和相对重量呈剂量依赖性增加。血清酶活性,即丙氨酸转氨酶和天冬氨酸转氨酶,在暴露于PFOA的小鼠中呈剂量依赖性增加。在组织病理学评估中,PFOA处理的小鼠肝脏显示出明显的肝细胞肿大和嗜酸性细胞质。在高剂量PFOA时,观察到多灶性凝固性和液化性坏死导致的弥漫性肝损伤。与肝脏的显著变化相反,肾脏几乎没有变化。PFOA未处理组和PFOA处理组小鼠的肾脏大小、相对重量、肾脏损伤生物标志物(血尿素氮、肌酐)以及组织病理学变化均无差异。总之,我们的结果表明PFOA对肝脏有毒性作用,但对肾脏无毒性作用。

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