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温室农民暴露于农药导致的肾小管功能障碍,通过一组肾脏损伤的分子生物标志物揭示。

Renal tubular dysfunction in greenhouse farmers exposed to pesticides unveiled by a panel of molecular biomarkers of kidney injury.

机构信息

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

Escuela Andaluza de Salud Pública, Granada, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain; Instituto de Investigación Biosanitaria, Granada (ibs.GRANADA), Spain; Andalusian Health and Environment Observatory (OSMAN), Granada, Spain.

出版信息

Environ Res. 2023 Dec 1;238(Pt 2):117200. doi: 10.1016/j.envres.2023.117200. Epub 2023 Sep 26.

Abstract

Growing evidence suggests that chronic exposure to pesticides may cause adverse effects on the health of the exposed population leading to organ-specific toxicity, including kidney damage. Traditional markers used to assess renal function (glomerular filtration rate (GFR), and serum creatinine and cystatin C -Cys-C-) are inadequate to evaluate a potential subclinical renal impairment linked to occupational exposure to pesticides, since levels above the upper limit of normal only occur when renal damage is very extensive. The use of more sensitive biomarkers is therefore needed. This study investigated novel urinary biomarkers of kidney function (microalbuminuria, osteopontin (OPN), trefoil factor 3 (TFF3), β-2-microglobulin, neutrophil gelatinase-associated lipocalin (NGAL), and Cys-C), together with the aforementioned traditional serum biomarkers, to assess potential kidney damage in farmers exposed to pesticides in an intensive agriculture setting. The study population consisted of 175 greenhouse workers and 91 healthy control subjects from Almeria (Southeastern Spain), a major hub of greenhouse agriculture. Data were collected at two different time-points of the same crop season: a period with greater pesticide use (high exposure period) and another with lower pesticide use (low exposure period). Significantly higher urinary levels of OPN and TFF3 were found in greenhouse workers than in controls, and in the high pesticide exposure period compared to that of low exposure. These changes suggest a subclinical tubular damage linked to pesticide exposure. In contrast, microalbuminuria, GFR, serum creatinine and Cys-C failed to be associated with pesticide exposure, suggesting that glomerular function was spared. Increased OPN and TFF3 levels over time may suggest a gradual progression from tubular dysfunction to chronic kidney disease in the exposed population.

摘要

越来越多的证据表明,长期接触农药可能对暴露人群的健康产生不良影响,导致特定器官毒性,包括肾脏损害。用于评估与职业性接触农药相关的潜在亚临床肾脏损害的传统肾功能标志物(肾小球滤过率(GFR)、血清肌酐和胱抑素 C-Cys-C-)不够充分,因为只有当肾脏损伤非常广泛时,水平才会超过正常值上限。因此,需要使用更敏感的生物标志物。本研究调查了新型肾脏功能生物标志物(微量白蛋白尿、骨桥蛋白(OPN)、三叶因子 3(TFF3)、β-2-微球蛋白、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和 Cys-C)以及上述传统血清标志物,以评估在集约化农业环境中接触农药的农民的潜在肾脏损伤。研究人群包括来自西班牙东南部阿尔梅里亚的 175 名温室工人和 91 名健康对照者,该地区是温室农业的主要中心。数据在同一作物季节的两个不同时间点收集:一个是农药使用较多的时期(高暴露期),另一个是农药使用较少的时期(低暴露期)。与对照组相比,温室工人的尿液 OPN 和 TFF3 水平明显更高,而且在高农药暴露期比低暴露期更高。这些变化表明与农药暴露相关的亚临床肾小管损伤。相比之下,微量白蛋白尿、GFR、血清肌酐和 Cys-C 与农药暴露无关,表明肾小球功能未受损。随着时间的推移,OPN 和 TFF3 水平的升高可能表明暴露人群的肾小管功能障碍逐渐进展为慢性肾脏病。

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