Chronic Exposure to Climbazole Induces Oxidative Stress and Sex Hormone Imbalance in the Testes of Male Zebrafish

• Published in: Chemical research in toxicology 2021-12, Vol.34 (12), p.2558-2566
• Main Authors: Liao, Xiao-Liang, Chen, Zhi-Feng, Zou, Ting, Lin, Zhi-Cheng, Chen, Xiao-Fan, Wang, Yujie, Qi, Zenghua, Cai, Zongwei
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Dose-Response Relationship, Drug; Gonadal Steroid Hormones - antagonists & inhibitors; Gonadal Steroid Hormones - biosynthesis; Imidazoles - administration & dosage; Imidazoles - pharmacology; Male; Molecular Structure; Oxidative Stress - drug effects; Spermatozoa - drug effects; Testis - drug effects; Testis - metabolism; Testis - pathology; Zebrafish
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/acs.chemrestox.1c00326

As the main active ingredient for the treatment of fungal infections, climbazole (CBZ) is commonly used in a variety of personal care products. After its use, CBZ enters the receiving environment directly or indirectly through domestic sewage. Its concentration can be up to several nanograms per liter in surface water. So far, the effects of CBZ on the reproductive system of female zebrafish have been systematically studied, but the potential toxicity mechanism of CBZ on male zebrafish still needs to be further explored. In this study, adult male zebrafish were exposed to CBZ at concentrations of 0.1, 10, and 1000 μg·L–1 for 28 days, and their testes were collected for histological, mass-spectrometry-based metabolomics, and biochemical analyses. We found that CBZ caused a significantly abnormal metabolism of purine and glutathione and triggered oxidative stress in zebrafish testes, thereby inducing testicular cell apoptosis. In addition, CBZ could inhibit the synthesis of essential sex hormones in the testis and thus reduce the sperm production. The conclusions of this study fill the data gap on the reproductive toxicity of CBZ to male zebrafish and highlight the ecotoxicological application of untargeted metabolomics in the biomarker discovery.