Bioconcentration, metabolism and effects of diphenhydramine on behavioral and biochemical markers in crucian carp (Carassius auratus)

- Diphenhydramine accumulated in different organs of crucian carp.
- Similar metabolites to those in mammals were observed in fish liver.
- Diphenhydramine induced biochemical and behavioral alterations in crucian carp.
- Diphenhydramine accumulation and oxidative stress were correlated with behavioral alterations.

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 7 d. 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.