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接触敌敌畏农药会改变大鼠腹侧前列腺的形态和脂质代谢。

Exposure to Dichlorvos pesticide alters the morphology of and lipid metabolism in the ventral prostate of rats.

作者信息

Quintino-Ottonicar Giovanna Galo, da Silva Laura Ribeiro, Maria Vinícius Luís Rocha da Silva, Pizzo Eleonora Malavolta, de Santana Ana Clara Pacheco, Lenharo Naíra Ruiz, Pinho Cristiane Figueiredo, Pereira Sergio

机构信息

Endocrine Disruptors Laboratory, School of Sciences, Department of Biological Sciences, São Paulo State University, Bauru, Brazil.

出版信息

Front Toxicol. 2023 Jul 4;5:1207612. doi: 10.3389/ftox.2023.1207612. eCollection 2023.

Abstract

Organophosphate pesticides are widely used in agriculture, leading to soil, water, and food contamination. Among these compounds is Dichlorvos [O,O-dimethyl O-(2,2-dichlorovinyl)phosphate, DDVP], which is listed as a highly toxic compound by the Environmental Protection Agency and World Health Organization. Exposure to DDVP can result in nervous, respiratory, hepatic, and reproductive abnormalities, in addition to endocrine disrupting, mutagenic, and carcinogenic effects. Little is known about the impacts of DDVP on the reprogramming of lipid metabolism, which is also associated with the development and progression of cancer, since the tumor cells need to recruit, capture, and use fatty acids to compose their building membranes. This study aimed to evaluate the influence of the pesticide DDVP on lipid metabolism in the prostate, after chemical induction by the carcinogen N-methyl-N-nitrosourea (MNU). For this, 32 Fischer rats aged 90 days were randomly divided into four experimental groups: Control, DDVP, MNU, and MNU + DDVP. The MNU and MNU + DDVP groups underwent chemical induction with MNU (15 mg/kg) and the DDVP and MNU + DDVP groups received a diet supplemented with DDVP (10 mg/kg). Histopathological analyses of the rat ventral prostate showed 100% incidence of epithelial hyperplasia in the MNU and MNU + DDVP groups. This finding was accompanied by an increase of the epithelial compartment in the MNU + DDVP group. Immunolocalization of important proteins linked to lipid metabolism has been established. In the MNU + DDVP group, Western blotting analyses pointed out an increased expression of the protein LIMP II (Lysosomal Integral Membrane Protein-II), which is correlated with the capture and distribution of lipids in tumor cells. Together, these results indicate that the association of a low dose of DDVP with MNU was able to promote alterations in the morphology and lipid metabolism of the rat ventral prostate, which may be related to tumor progression in this organ.

摘要

有机磷酸酯类农药在农业中广泛使用,导致土壤、水和食物受到污染。这些化合物中包括敌敌畏[O,O-二甲基-O-(2,2-二氯乙烯基)磷酸酯,DDVP],它被美国环境保护局和世界卫生组织列为高毒化合物。接触敌敌畏除了会产生内分泌干扰、致突变和致癌作用外,还会导致神经、呼吸、肝脏和生殖异常。由于肿瘤细胞需要摄取、捕获和利用脂肪酸来构建细胞膜,因此关于敌敌畏对脂质代谢重编程的影响知之甚少,而脂质代谢也与癌症的发生和发展有关。本研究旨在评估在致癌物N-甲基-N-亚硝基脲(MNU)化学诱导后,农药敌敌畏对前列腺脂质代谢的影响。为此,将32只90日龄的Fischer大鼠随机分为四个实验组:对照组、敌敌畏组、MNU组和MNU+敌敌畏组。MNU组和MNU+敌敌畏组用MNU(15mg/kg)进行化学诱导,敌敌畏组和MNU+敌敌畏组接受添加了敌敌畏(10mg/kg)的饮食。大鼠腹侧前列腺的组织病理学分析显示,MNU组和MNU+敌敌畏组上皮增生的发生率为100%。这一发现伴随着MNU+敌敌畏组上皮细胞区室的增加。已确定了与脂质代谢相关的重要蛋白质的免疫定位。在MNU+敌敌畏组中,蛋白质印迹分析指出溶酶体整合膜蛋白II(LIMP II)的表达增加,这与肿瘤细胞中脂质的捕获和分布相关。总之,这些结果表明低剂量的敌敌畏与MNU联合能够促进大鼠腹侧前列腺的形态和脂质代谢改变,这可能与该器官的肿瘤进展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b89d/10352615/ab6b7e673ebd/ftox-05-1207612-g001.jpg

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