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BioMed Research International
Volume 2017, Article ID 5829756, 8 pages
https://doi.org/10.1155/2017/5829756
Research Article

Effects of Fungicides on Rat’s Neurosteroid Synthetic Enzymes

1Department of Pharmacy, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325200, China
2Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
3Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China

Correspondence should be addressed to Ren-Shan Ge; moc.oohay@eg_r

Received 16 March 2017; Revised 21 May 2017; Accepted 4 June 2017; Published 24 July 2017

Academic Editor: Jane Hanrahan

Copyright © 2017 Xiuwei Shen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Exposure to environmental endocrine disruptors may interfere with nervous system’s activity. Fungicides such as tebuconazole, triadimefon, and vinclozolin have antifungal activities and are used to prevent fungal infections in agricultural plants. In the present study, we studied effects of tebuconazole, triadimefon, and vinclozolin on rat’s neurosteroidogenic 5α-reductase 1 (5α-Red1), 3α-hydroxysteroid dehydrogenase (3α-HSD), and retinol dehydrogenase 2 (RDH2). Rat’s 5α-Red1, 3α-HSD, and RDH2 were cloned and expressed in COS-1 cells, and effects of these fungicides on them were measured. Tebuconazole and triadimefon competitively inhibited 5α-Red1, with IC50 values of 8.670 ± 0.771 × 10−6 M and 17.390 ± 0.079 × 10−6 M, respectively, while vinclozolin did not inhibit the enzyme at 100 × 10−6 M. Triadimefon competitively inhibited 3α-HSD, with IC50 value of 26.493 ± 0.076 × 10−6 M. Tebuconazole and vinclozolin weakly inhibited 3α-HSD, with IC50 values about 100 × 10−6 M, while vinclozolin did not inhibit the enzyme even at 100 × 10−6 M. Tebuconazole and triadimefon weakly inhibited RDH2 with IC50 values over 100 × 10−6 M and vinclozolin did not inhibit this enzyme at 100 × 10−6 M. Docking study showed that tebuconazole, triadimefon, and vinclozolin bound to the steroid-binding pocket of 3α-HSD. In conclusion, triadimefon potently inhibited rat’s neurosteroidogenic enzymes, 5α-Red1 and 3α-HSD.