Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by isothiazolinone-based disinfectants: Insights into mechanism and implications for hormonal homeostasis

Chuhang Chi; Chaochao Gong; Yunbing Tang; He Zhu; Qian Zhang; Yang Zhu; Shaowei Wang; Ren-shan Ge; Xiaoheng Li

doi:10.1016/j.ecoenv.2025.118248

Ecotoxicology and Environmental Safety (Jun 2025)

Suppression of human and rat 17β-hydroxysteroid dehydrogenase 1 by isothiazolinone-based disinfectants: Insights into mechanism and implications for hormonal homeostasis

Chuhang Chi,
Chaochao Gong,
Yunbing Tang,
He Zhu,
Qian Zhang,
Yang Zhu,
Shaowei Wang,
Ren-shan Ge,
Xiaoheng Li

Affiliations

Chuhang Chi: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, Zhejiang 325027, China; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Chaochao Gong: Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Yunbing Tang: Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
He Zhu: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, Zhejiang 325027, China; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Qian Zhang: Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Yang Zhu: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, Zhejiang 325027, China; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Shaowei Wang: Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China
Ren-shan Ge: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, Zhejiang 325027, China; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Male Health and Environment of Wenzhou, Zhejiang Province 325000, China; Correspondence to: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou, Zhejiang 325000, China.
Xiaoheng Li: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Pediatric Anesthesiology, Ministry of Education, Wenzhou, Zhejiang 325027, China; Key Laboratory of Precision Anesthesiology of Zhejiang Province, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Obstetrics and Gynecology, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Key Laboratory of Male Health and Environment of Wenzhou, Zhejiang Province 325000, China; Correspondence to: Department of Anesthesiology and Perioperative Medicine, the Second Affiliated Hospital and Yuying Children’s Hospital, Wenzhou, Zhejiang 325000, China.

DOI: https://doi.org/10.1016/j.ecoenv.2025.118248
Journal volume & issue: Vol. 297
p. 118248

Abstract

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Isothiazolinone disinfectants constitute a class of broad-spectrum antimicrobial agents due to the pandemic of COVID-19. The aim of this study was to assess the impacts of six distinct isothiazolinone disinfectants on the activity of 17β-hydroxysteroid dehydrogenase 1 (17β-HSD1) in humans and rats, as well as on BeWo cells. We identified IC50 with 4,5-dichloro-2-octyl-1,2-thiazol-3-one exhibiting the most potent inhibition (8.09 μM for human 17β-HSD1) and 5-chloro-2-methyl-1,2-thiazol-3-one showing the weak inhibition (81.94 μM for human 17β-HSD1) and these chemicals can potently inhibit estradiol production at ≥ 1 μM. Additionally, 4,5-dichloro-2-octyl-1,2-thiazol-3-one and 2-octyl-1,2-thiazol-3-one inhibited rat 17β-HSD1 at IC50 concentrations of 20.53 and 32.47 μM, respectively. Through mode action analyses, these compounds were found to exert mixed inhibition. Computational docking simulations revealed that isothiazolinone disinfectants interact with the NADPH binding domains of the two enzymes. Bivariate correlation analysis confirmed negative relationships between physicochemical properties such as LogP and heavy atoms, and half maximum inhibition concentrations of these chemicals. 3D-QSAR analysis revealed the presence of hydrophobic and hydrogen bond regions and both positively contribute to the binding. In conclusion, isothiazolinone disinfectants repress human and rat 17β-HSD1, depending on their hydrophobicity and hydrogen bonds.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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