School of Public Health, Seoul National University, 599 Gwanak-ro, Gwanak, Seoul, 151-742, Republic of Korea.
J Hazard Mater. 2010 Oct 15;182(1-3):494-502. doi: 10.1016/j.jhazmat.2010.06.059. Epub 2010 Jun 19.
Pharmaceuticals in the environment are of growing concern for their potential consequences on human and ecosystem health. Alterations in the endocrine system in humans or wildlife are of special interest because these alterations could eventually lead to changes in reproductive fitness. Using the H295R cell line, the potential endocrine disrupting effects of six pharmaceuticals including diclofenac, erythromycin, sulfamethazine, sulfathiazole, oxytetracycline, and chlortetracycline were investigated. After exposure to each target pharmaceutical for 48 h, production of 17beta-estradiol (E2) and testosterone (T), aromatase (CYP19) enzyme activity, or expression of steroidogenic genes were measured. Concentrations of E2 in blood plasma were determined in male Japanese medaka fish after 14 d exposure to sulfathiazole, oxytetracycline, or chlortetracycline. Among the pharmaceuticals studied, sulfathiazole, oxytetracycline and chlortetracycline all significantly affected E2 production by H295R cells. This mechanism of the effect was enhanced aromatase activity and up-regulation of mRNAs for CYP17, CYP19, and 3betaHSD, all of which are important components of steroidogenic pathways. Sulfathiazole was the most potent compound affecting steroidogenesis in H295R cells, followed by chlortetracycline and oxytetracycline. Sulfathiazole significantly increased aromatase activity at 0.2 mg/l. In medaka fish, concentrations of E2 in plasma increased significantly during 14-d exposure to 50 or 500 mg/l sulfathiazole, or 40 mg/l chlortetracycline. Based on the results of this study, certain pharmaceuticals could affect steroidogenic pathway and alter sex hormone balance. Concentrations of the pharmaceuticals studied that have been reported to occur in rivers of Korea are much less than the thresholds for effects on the endpoints studied here. Thus, it is unlikely that these pharmaceuticals are causing adverse effects on fish in those rivers.
环境中的药品越来越受到关注，因为它们可能对人类和生态系统健康产生影响。特别关注的是人类或野生动物内分泌系统的改变，因为这些改变最终可能导致生殖适应性的变化。本研究使用 H295R 细胞系，研究了六种药品（包括双氯芬酸、红霉素、磺胺甲噁唑、磺胺噻唑、土霉素和金霉素）的潜在内分泌干扰作用。将每种靶标药品暴露于细胞 48 小时后，测量 17β-雌二醇（E2）和睾酮（T）的产生、芳香酶（CYP19）酶活性或类固醇生成基因的表达。在雄性日本青鳉鱼中，在暴露于磺胺噻唑、土霉素或金霉素 14 天后，测定血浆中 E2 的浓度。在所研究的药品中，磺胺噻唑、土霉素和金霉素均显著影响 H295R 细胞中 E2 的产生。这种作用机制是通过增强芳香酶活性和上调 CYP17、CYP19 和 3βHSD 的 mRNA 表达来实现的，这些都是类固醇生成途径的重要组成部分。磺胺噻唑是影响 H295R 细胞类固醇生成的最有效化合物，其次是金霉素和土霉素。磺胺噻唑在 0.2mg/L 时显著增加芳香酶活性。在青鳉鱼中，在暴露于 50 或 500mg/L 磺胺噻唑或 40mg/L 金霉素的 14 天期间，血浆中 E2 的浓度显著增加。根据本研究的结果，某些药品可能会影响类固醇生成途径并改变性激素平衡。在所研究的药品中，已报道在韩国河流中存在的浓度远低于对本研究中研究终点产生影响的阈值。因此，这些药品不太可能对这些河流中的鱼类产生不良影响。
