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采用基于核磁共振的代谢组学方法研究五氯苯酚暴露对雄性和雌性的毒性。

Toxicity of Pentachlorophenol Exposure on Male and Female Investigated Using NMR-Based Metabolomics Approach.

作者信息

Singh Sonam, Yadav Sachin, Chaube Radha, Kumar Dinesh

机构信息

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India.

Department of Chemistry, Integral University, Lucknow 226026, India.

出版信息

ACS Omega. 2025 Feb 11;10(7):6368-6384. doi: 10.1021/acsomega.4c03407. eCollection 2025 Feb 25.

Abstract

Pentachlorophenol (PCP) is one of the most common chlorophenols utilized in numerous industrial processes, including the production of dyes, pesticides, wood preservatives, disinfectants, antiseptics, and medicines because it has fungicidal and bactericidal characteristics. Previous studies on catfish () revealed that PCP acts as a potent endocrine disruptor and also causes behavioral changes in a concentration-dependent manner. However, the toxicological effects of PCP have not been compared between male and female catfish. The present study aims to investigate the toxic effects of PCP on catfish through histopathological changes, oxidative stress, and serum metabolomics after 60 days of exposure. Chronic exposure to sublethal concentrations of PCP resulted in significant histopathological alterations in the liver and gonad, including leukocyte infiltration, hepatocyte degeneration, follicular layer dissolution, and abnormal sperm distribution. Increased levels of lipid peroxidation and hydrogen peroxide, along with decreased antioxidant enzyme activity, were observed in PCP-exposed groups. A H NMR-based metabolomics approach was employed to investigate the toxic effects of PCP on catfish serum, revealing alterations in various metabolites, including amino acids, organic acids, glucose, cholesterol, and neurotransmitters, in a dose-dependent manner. Multivariate partial least-squares discriminant analysis (PLS-DA) identified metabolic changes associated with oxidative stress, disruption in hormone synthesis and reproduction, disturbance in osmoregulation and membrane stabilization, energy metabolism disorder, amino acid metabolism disorder, and neurotransmitter imbalance in PCP-exposed catfish. This study demonstrates the efficacy of metabolomics in elucidating the toxicity and underlying mechanisms of wood preservatives like PCP, providing valuable insights for risk assessment in toxicology research. Overall, these findings contribute to our understanding of the toxicological effects of PCP exposure on aquatic organisms and highlight the potential of histology, oxidative stress, and metabolomics in assessing environmental contaminants' risks.

摘要

五氯苯酚(PCP)是众多工业过程中最常用的氯酚之一,用于染料、农药、木材防腐剂、消毒剂、防腐剂和药品的生产,因为它具有杀菌和抑菌特性。先前对鲶鱼()的研究表明,PCP是一种强效内分泌干扰物,还会以浓度依赖的方式引起行为变化。然而,尚未对雄性和雌性鲶鱼之间PCP的毒理学效应进行比较。本研究旨在通过暴露60天后的组织病理学变化、氧化应激和血清代谢组学来研究PCP对鲶鱼的毒性作用。长期暴露于亚致死浓度的PCP会导致肝脏和性腺出现明显的组织病理学改变,包括白细胞浸润、肝细胞变性、卵泡层溶解和精子分布异常。在暴露于PCP的组中观察到脂质过氧化和过氧化氢水平升高,同时抗氧化酶活性降低。采用基于核磁共振氢谱的代谢组学方法研究PCP对鲶鱼血清的毒性作用,结果显示各种代谢物(包括氨基酸、有机酸、葡萄糖、胆固醇和神经递质)发生了剂量依赖性变化。多变量偏最小二乘判别分析(PLS-DA)确定了与暴露于PCP的鲶鱼氧化应激、激素合成和繁殖紊乱、渗透调节和膜稳定性干扰、能量代谢紊乱、氨基酸代谢紊乱以及神经递质失衡相关的代谢变化。本研究证明了代谢组学在阐明PCP等木材防腐剂的毒性及其潜在机制方面的有效性,为毒理学研究中的风险评估提供了有价值的见解。总体而言,这些发现有助于我们了解PCP暴露对水生生物的毒理学效应,并突出了组织学、氧化应激和代谢组学在评估环境污染物风险方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e93a/11866196/a67509225451/ao4c03407_0001.jpg

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