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有机氯农药通过氧化应激诱导甲状腺肿瘤;一项体内和计算机模拟研究。

Organochlorine pesticides induce thyroid tumors through oxidative stress; an in vivo and in silico study.

作者信息

Salimi Fouzieh, Asadikaram Gholamreza, Abolhassani Moslem, Pourfarjam Yasin, Nejad Hamid Zeynali, Abbasi-Jorjandi Mojtaba, Sanjari Mojgan

机构信息

Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman, Iran.

Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Environ Sci Pollut Res Int. 2023 Mar;30(15):45046-45066. doi: 10.1007/s11356-023-25304-1. Epub 2023 Jan 26.

Abstract

Thyroid disease is one of the most common endocrine problems around the world. Among the numerous factors, exposure to environmental elements such as pesticides is associated with an increase in the incidence of thyroid disorders. The aim of the present study was to investigate the role of organochlorine pesticides (OCPs) in induction of oxidative stress (OS) and development of thyroid tumors. This case-control study was conducted on 61 patients with papillary thyroid carcinoma (PTC), 70 patients with benign thyroid nodules (BTN), and 73 healthy individuals as control. Seven derived OCPs residues measured by gas chromatography (GC), and enzyme activities of acetylcholinesterase (AChE), superoxide dismutase3 (SOD3), catalase (CAT), glutathione peroxidase3 (GPx3) and paraoxonase1 (PON1) and also, non-enzymatic antioxidant including; malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC), and nitric oxide (NO) biomarkers in all participants were investigated. Furthermore, all of the above enzymes were docked against measured OCPs. The results revealed that β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4-DDT, and 4,4-DDT levels along with MDA, NO, and PC levels were elevated, while AChE, SOD3, GPx3, CAT, and PON1 activities and TAC levels were decreased in the PTC and BTN groups compared with the control group. Therefore, OCPs might play a role in the development of thyroid tumors through several mechanisms including generation of OS. Importantly, in silico analysis confirmed the in vivo findings.

摘要

甲状腺疾病是全球最常见的内分泌问题之一。在众多因素中,接触农药等环境因素与甲状腺疾病发病率的增加有关。本研究的目的是调查有机氯农药(OCPs)在诱导氧化应激(OS)和甲状腺肿瘤发生中的作用。本病例对照研究对61例甲状腺乳头状癌(PTC)患者、70例甲状腺良性结节(BTN)患者和73名健康个体作为对照进行。通过气相色谱法(GC)测定了7种衍生的OCPs残留量,并研究了所有参与者体内乙酰胆碱酯酶(AChE)、超氧化物歧化酶3(SOD3)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶3(GPx3)和对氧磷酶1(PON1)的酶活性,以及非酶抗氧化剂,包括丙二醛(MDA)、总抗氧化能力(TAC)、蛋白质羰基(PC)和一氧化氮(NO)生物标志物。此外,将上述所有酶与测得的OCPs进行对接。结果显示,与对照组相比,PTC组和BTN组中β-六氯环己烷、γ-六氯环己烷、2,4-滴滴伊、4,4-滴滴伊、2,4-滴滴涕和4,4-滴滴涕的水平以及MDA、NO和PC的水平升高,而AChE、SOD3、GPx3、CAT和PON1的活性以及TAC水平降低。因此,OCPs可能通过包括产生OS在内的多种机制在甲状腺肿瘤的发生中发挥作用。重要的是,计算机分析证实了体内研究结果。

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