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有机氯农药血浆水平与肿瘤坏死因子-α:印度北部人群发生获得性再生障碍性贫血的潜在危险因素

Plasma Levels of Organochlorine Pesticides and Tumor Necrosis Factor-Alpha: A Potential Risk Factor for Developing Acquired Aplastic Anemia in the North Indian Population.

作者信息

Goel Charu, Kumar Nidhish, Tripathi Anil K, Tiwari Sunita, Shrivastava Ashutosh, Shukla Saurabh, Mishra Alok, Srivastava Anshuman

机构信息

Physiology, Muzaffarnagar Medical College & Hospital, Muzaffarnagar, IND.

Physiology, King George's Medical University, Lucknow, IND.

出版信息

Cureus. 2023 Sep 28;15(9):e46122. doi: 10.7759/cureus.46122. eCollection 2023 Sep.

DOI:10.7759/cureus.46122
PMID:37900403
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10612378/
Abstract

Background Pesticide exposure might have a contributory role in the development of acquired aplastic anemia (AA). However, the precise mechanisms of pesticide-induced AA remain unknown. In this case-control study, we conducted a comparative analysis of plasma levels of organochlorine pesticides (OCP) and tumor necrosis factor-alpha (TNF-alpha) between Indian patients diagnosed with AA and an age- and sex-matched control group. Methods This is an observational case-control study conducted at a tertiary care hospital in North India. In this study, 90 subjects were included, out of which 45 were diagnosed with AA according to the criteria of the International Agranulocytosis and Aplastic Anemia Study. Cases were compared with 45 controls. A trained interviewer gave all study subjects a questionnaire to collect data regarding demographic details, exposure to pesticides, and clinical history. Physical examination and routine laboratory investigations of each subject were performed. Both cases and controls were tested for their plasma levels of organochlorines as per established protocol by gas chromatography-mass spectrometry. TNF-alpha level was measured by enzyme-linked immunosorbent assay in each subject. Results There was a significant increase in plasma levels of delta hexachlorocyclohexane (delta HCH) (p = 0.02) and heptachlor (p = 0.00) in patients with AA as compared to controls. We observed nonsignificant trends towards higher levels of beta HCH (p = 0.643), aldrin (p = 0.399), and p,p'-Dichlorodiphenyltrichloroethane (p,p'-DDT) (p = 0.453) in patients with AA when compared to the controls. There were significantly higher TNF-alpha levels (p = 0.024) in cases as compared to the controls. Conclusion Our study concludes that patients with AA exhibited higher levels of delta-HCH, heptachlor, and TNF-alpha in comparison to the control group. There is a significant positive correlation of TNF alpha with OCPs (alpha HCH, lindane, delta HCH, heptachlor, aldrin, p,p'- DDD, and methoxychlor pesticides). These organochlorines may have accumulated in the fatty tissue of bone marrow because of their lipophilic nature. This suggests that they might have served as a neoantigen to trigger an increase in TNF-alpha production, which may have led to disrupted bone marrow function through cell-mediated immunity, leading to AA.

摘要

背景 农药暴露可能在获得性再生障碍性贫血(AA)的发生中起一定作用。然而,农药诱导AA的确切机制仍不清楚。在这项病例对照研究中,我们对印度诊断为AA的患者与年龄和性别匹配的对照组之间的血浆有机氯农药(OCP)水平和肿瘤坏死因子-α(TNF-α)进行了比较分析。

方法 这是一项在印度北部一家三级护理医院进行的观察性病例对照研究。本研究纳入了90名受试者,其中45名根据国际粒细胞缺乏症和再生障碍性贫血研究的标准被诊断为AA。将病例与45名对照进行比较。一名经过培训的访谈员向所有研究受试者发放问卷,以收集有关人口统计学细节、农药暴露和临床病史的数据。对每个受试者进行体格检查和常规实验室检查。按照既定方案,通过气相色谱-质谱法对病例组和对照组的血浆有机氯水平进行检测。通过酶联免疫吸附测定法测量每个受试者的TNF-α水平。

结果 与对照组相比,AA患者血浆中δ-六氯环己烷(δ-HCH)(p = 0.02)和七氯(p = 0.00)水平显著升高。与对照组相比,我们观察到AA患者的β-HCH(p = 0.643)、艾氏剂(p = 0.399)和对,对'-二氯二苯三氯乙烷(p,p'-DDT)(p = 0.453)水平有升高趋势,但无统计学意义。与对照组相比,病例组的TNF-α水平显著更高(p = 0.024)。

结论 我们的研究得出结论,与对照组相比,AA患者的δ-HCH、七氯和TNF-α水平更高。TNF-α与OCPs(α-HCH、林丹、δ-HCH、七氯、艾氏剂、对,对'-滴滴滴和甲氧滴滴涕农药)之间存在显著正相关。这些有机氯可能因其亲脂性而在骨髓脂肪组织中蓄积。这表明它们可能作为新抗原触发TNF-α产生增加,这可能通过细胞介导的免疫导致骨髓功能紊乱,进而导致AA。