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评价职业暴露于农药的温室工人的传统和非传统肝毒性生物标志物。

Evaluation of conventional and non-conventional biomarkers of liver toxicity in greenhouse workers occupationally exposed to pesticides.

机构信息

University of Almería School of Health Sciences, Almería, Spain.

Department of Legal Medicine and Toxicology, University of Granada School of Medicine, Granada, Spain.

出版信息

Food Chem Toxicol. 2021 May;151:112127. doi: 10.1016/j.fct.2021.112127. Epub 2021 Mar 13.

Abstract

The liver plays a prominent role in maintenance of homeostasis and is the major organ for xenobiotic metabolism, including pesticides. Conventional liver function tests are widely used to assess hepatocellular and biliary system dysfunction by measuring serum levels of aminotransferases (ALT, AST) and cholestasis enzymes (alkaline phosphatase -ALP- and γ-glutamyl transferase -GGT-), respectively. Although these tests are not entirely specific for liver damage, their specificity increases when measured concurrently, but still have limited usefulness to predict early liver dysfunction. Hence, non-conventional biomarkers may have a better performance for the early detection of biochemical hepatotoxicity with a greater specificity and sensitivity. A cross-sectional study with a follow-up component was conducted on 175 greenhouse workers regularly exposed to pesticides under integrated production system, and 91 controls living in the same geographical area. All individuals were evaluated for conventional (ALT, AST, ALP, GGT) and non-conventional biomarkers of hepatotoxicity (ornithine transcarbamylase (-OTC-), Arginase-1 -ARG1- and glutathione S-transferase alpha -GSTα-) over two periods of the same crop season, one of high pesticide exposure and other of low exposure. A slight increase in AST was observed in greenhouse workers relative to controls, suggestive of subtle hepatocellular toxicity. Although ALP, ARG1 and GST-α levels were decreased in greenhouse workers, this might be related to a potential homeostatic mechanism that regulates their expression. Altogether, these findings do not represent unambiguous evidence of liver dysfunction (e.g., hepatocellular or biliary system impairment) but may be the result of the low-toxicity pesticides used by greenhouse workers.

摘要

肝脏在维持体内平衡方面起着重要作用,是代谢外来物质(包括农药)的主要器官。传统的肝功能测试广泛用于通过测量血清中转氨酶(ALT、AST)和胆汁淤积酶(碱性磷酸酶-ALP-和γ-谷氨酰转移酶-GGT-)的水平来评估肝细胞和胆道系统功能障碍。尽管这些测试并非完全特异性地用于肝脏损伤,但当同时测量时,它们的特异性会增加,但仍然对预测早期肝功能障碍的作用有限。因此,非传统生物标志物可能具有更好的早期检测生化性肝毒性的性能,具有更高的特异性和敏感性。对在综合生产系统下定期接触农药的 175 名温室工人和居住在同一地理区域的 91 名对照进行了一项具有随访部分的横断面研究。在同一作物季节的两个时期对所有个体进行常规(ALT、AST、ALP、GGT)和非传统肝毒性生物标志物(鸟氨酸转氨甲酰酶(-OTC-)、精氨酸酶-1(ARG1)和谷胱甘肽 S-转移酶 alpha(GSTα))进行评估,一个时期是高农药暴露期,另一个时期是低暴露期。与对照组相比,温室工人的 AST 略有升高,提示存在轻微的肝细胞毒性。尽管温室工人的 ALP、ARG1 和 GST-α 水平降低,但这可能与调节其表达的潜在体内平衡机制有关。总之,这些发现并不代表明确的肝功能障碍证据(例如,肝细胞或胆道系统损伤),但可能是温室工人使用低毒性农药的结果。

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