Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
Sci Total Environ. 2016 Feb 15;544:400-9. doi: 10.1016/j.scitotenv.2015.11.132. Epub 2015 Dec 4.
Diphenhydramine (DPH), an antihistamine used to alleviate human allergies, is widespread in aquatic environments. However, little is known about the biochemical and behavioral effects of DPH on non-target aquatic animals. In the present study, the tissue distribution, bioconcentration, metabolism, biochemical and behavioral effects were investigated in crucian carp (Carassius auratus) exposed to various concentrations of DPH (0.84, 4.23, 21.7 and 112 μg L(-1)) for 7d. DPH can accumulate in crucian carp, and high concentrations have been observed in the liver and brain with maximum bioconcentration factors of 148 and 81.6, respectively. A portion of the absorbed DPH was metabolized by the crucian carp to N-demethyl DPH and N,N-didemethyl DPH via N-demethylation. Direct fluorimetric assay was employed to assess metabolic activity, while oxidative stress and neurotransmission biomarkers were determined by Diagnostic Reagent Kits. DPH was found to increase hepatic 7-ethoxyresorufin O-deethylase activity in crucian carp with maximal induction of 119%. Concerning the oxidative stress status, DPH significantly inhibited superoxide dismutase (SOD, 37-58%) and glutathione S-transferase (GST, 43-65%) activities and led to a significant increase in malondialdehyde (MDA, 67-140%) levels and catalase (CAT, 38-143%) and glutathione peroxidase (GPx, 39-189%) activities in fish liver. Brain acetylcholinesterase activity was also induced in DPH-exposed crucian carp with maximal induction of 174%. In addition, shoaling was significantly enhanced, while swimming activity and feeding rates were markedly suppressed at DPH concentrations equal to or higher than 21.7 μg L(-1). Furthermore, significant correlations were found between oxidative stress biomarkers (SOD, CAT, GPx, GST and MDA) and behavioral parameters. Collectively, our results confirmed that DPH can accumulate and be metabolized in fish and exert a negative effect at different levels of biological organization.
苯海拉明（DPH）是一种用于缓解人类过敏的抗组胺药，广泛存在于水生环境中。然而，人们对 DPH 对非靶标水生动物的生化和行为影响知之甚少。在本研究中，研究了鲫鱼（Carassius auratus）暴露于不同浓度的 DPH（0.84、4.23、21.7 和 112 μg/L）7d 后，组织分布、生物浓缩、代谢、生化和行为效应。DPH 可以在鲫鱼中积累，并且在肝脏和大脑中观察到高浓度，最大生物浓缩因子分别为 148 和 81.6。吸收的 DPH 有一部分被鲫鱼代谢为 N-去甲基 DPH 和 N,N-二去甲基 DPH 通过 N-去甲基化。直接荧光法用于评估代谢活性，而氧化应激和神经递质生物标志物则通过诊断试剂试剂盒来确定。DPH 被发现会增加鲫鱼肝脏中的 7-乙氧基香豆素 O-去乙基酶活性，最大诱导率为 119%。关于氧化应激状态，DPH 显著抑制超氧化物歧化酶（SOD，37-58%）和谷胱甘肽 S-转移酶（GST，43-65%）的活性，并导致丙二醛（MDA，67-140%）水平显著增加，以及鱼肝脏中的过氧化氢酶（CAT，38-143%）和谷胱甘肽过氧化物酶（GPx，39-189%）的活性增加。暴露于 DPH 的鲫鱼脑中的乙酰胆碱酯酶活性也被诱导，最大诱导率为 174%。此外，在 DPH 浓度等于或高于 21.7 μg/L 时，鱼群行为显著增强，而游泳活动和摄食率则明显受到抑制。此外，还发现氧化应激生物标志物（SOD、CAT、GPx、GST 和 MDA）与行为参数之间存在显著相关性。总之，我们的研究结果证实 DPH 可以在鱼类中积累和代谢，并在不同水平的生物组织中产生负面影响。
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