title: Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus).
abstract: 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.
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China. Electronic address: ghlu@hhu.edu.cn.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Lu
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
authors.forename: Kangkang
authors.initials: K
authors.lastname: Hou
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
authors.forename: Donghong
authors.initials: D
authors.lastname: Qin
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Key Laboratory of Integrated Regulation and Resources Development of Shallow Lakes of Ministry of Education, College of Environment, Hohai University, Nanjing 210098, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002347:Carps / Q000502:physiology*; D002374:Catalase / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004155:Diphenhydramine / Q000378:metabolism / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
chemical_list: D015415:Biomarkers; D014874:Water Pollutants, Chemical; D004155:Diphenhydramine; D002374:Catalase; D005979:Glutathione Peroxidase; D019363:Cytochrome P-450 CYP1A1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase
keywords: Antioxidant enzymes; Behavior; Bioconcentration; Diphenhydramine; Metabolism