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  • angiotensin receptor blockers Following DEX exposure the lev

    2020-11-20

    Following DEX exposure, the levels of CYP1A1 protein and activity remained unchanged, as seen in our previous in vitro study (Burkina et al., 2013). Dasmahapatra and Lee (1993) reported that 3.9μgL−1 DEX, similar to our highest tested concentration, did not change CYP1A1 protein content. An angiotensin receptor blockers increase in CYP3A protein content can be related to an adaptive mechanism of fish to DEX exposure. Immunoblotting data did not support the CYP450 activity data. CYP3A-like protein level was increased only at 3ngL−1 DEX, but not for other doses. This study showed that treatment with the same dose of DEX did not cause a change in the activity of BFCOD or BQOD (Fig. 2). In this study, the CYP2E1-like protein was not detected using several angiotensin receptor blockers against human and rat epitopes; however the CYP2E1 protein level was successfully determined and responded to carbon tetrachloride treatment in common carp liver (Jia et al., 2014). In future studies, it could be desirable to develop CYP2E1 antibodies against fish CYP2E1. A number of in vitro data have been reported for the effects of DEX on mammalian and fish CYP450 systems, but data from in vivo studies remains limited. It is important to investigate the effects of DEX at concentrations that commonly occur in the aquatic environment to mimic its possible interaction with fish-specific protein targets. Here, we tested the effects of low levels of residual DEX on specific pharmacological targets in fish and found that DEX can modify CYP450 activity in rainbow trout. We also clearly showed that DEX induces hepatic CYP3A-like proteins. This observation is important because there may be further interactions of environmentally relevant DEX concentrations with cellular recovery mechanisms and non-investigated xenobiotic-metabolizing proteins in fish. However, treatment of juvenile rainbow trout with DEX failed to demonstrate a clear and significant effect at high concentrations. In actual conditions, combinations of DEX with other glucocorticoids can raise synergistic actions of this key xenobiotic detoxification pathway.
    Conflict of interest statement
    Acknowledgement The study was financially supported by the Ministry of Education, Youth and Sports of the Czech Republic – projects “CENAKVA” (No. CZ.1.05/2.1.00/01.0024) and “CENAKVA II” (No. LO1205 under the NPU I program), by the Grant Agency of the University of South Bohemia in Ceske Budejovice (No. 087/2013/Z) and by the Czech Science Foundation (No. P503/11/1130). Individual CYP450 activities were analysed at Swedish University of Agricultural sciences, NJ Faculty. We also thank American Manuscript Editors for editing the English manuscript.
    Introduction 3-Methylindole (3MI), also known as skatole, is a naturally occurring substance found in mammalian faeces, cruciferous vegetables, beetroot and nectrandra wood. 3MI receives steady attention due to its wide range of biological effects (Hanafy and Bogan, 1982, Babol et al., 1998, Diaz and Squires, 2000). Previous studies have focused on the potential involvement of 3MI in several physiological processes in mammals. However, little attention was paid to the potential ecotoxicological consequences of this natural compound. The occurrence of 3MI in aquatic environments may be a cause for concern, mainly due to its significant load in wastewater. The presence of 3MI in aquatic environments is at least partly due to animal manure and anthropogenic waste. The discharge of untreated municipal wastewater during storm water overflow in heavy rain often delivers odorous volatile aromatic compounds such as 3MI to recipients. The surface runoff of liquid manure from livestock breeding facilities significantly contributes to pollution of surface water by 3MI. Improper application of liquid manure often used to fertilize agricultural fields increases risk of surface water contamination by this widely spread aromatic pollutant (Schüssler and Nitschke, 1999). Monitoring has indicated the presence of 3MI in contaminated groundwater (Smital et al., 2011, Yan et al., 2011, Gruchlik et al., 2013) and in the skin of fish from sites polluted by untreated wastewater (Schüssler and Nitschke, 1999).