Departamento de Fisiología, Instituto de Biociências, Universidade de São Paulo, 05508-090 São Paulo, Brazil.
Laboratório de Química Ambiental, Departamento de Química Analítica, Instituto de Química - Universidad de Campinas, 13086-970 Campinas, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2024 Apr;278:109846. doi: 10.1016/j.cbpc.2024.109846. Epub 2024 Feb 4.
Diclofenac (DCF) and ibuprofen (IBU) are pharmaceutical compounds frequently detected in aquatic compartments worldwide. Several hazard effects including developmental abnormalities and redox balance impairment have been elucidated in aquatic species, but multiple endocrine evaluations are scarce. Therefore, the present study aimed to assess the disruptive physiological effects and toxicity of DCF and IBU isolated and combined, using females of the native freshwater teleost Astyanax lacustris. In regards to NSAIDs bioavailability, the results showed absence of degradation of IBU and DCF after 7 days of exposure. IBU LC for A. lacustris was 137 mgL and females exposed to IBU isolated increased thyroxine (T) concentration at 24 h and decreased after 96 h; DCF exposure decreased triiodothyronine (T3) concentration at 96 h. Circulating levels of 17β-estradiol (E), cortisol (F) and testosterone (T) were not affected by any treatment. HPG and HPI axis genes fshβ, pomc and vtg were upregulated after 24 h of IBU exposure, and dio2 was downregulated in DCF fish exposed group after 96 h compared to the mixture. Protein concentration was reduced in muscle and increased in the liver by DCF and mixtures exposures at 24 h; while liver lipids were increased in the mixture groups after 96 h. The study point out the capacity of NSAIDs to affect endocrine endpoints in A. lacustris females and induce changes in energetic substrate content after acute exposure to isolated and mixed NSAIDs treatments. Lastly, the present investigation brings new insights into the toxicity and endocrine disruptive activity of NSAIDs in Latin America teleost species and the aquatic environment.
双氯芬酸 (DCF) 和布洛芬 (IBU) 是全球水生环境中经常检测到的药物化合物。已经在水生物种中阐明了包括发育异常和氧化还原平衡受损在内的几种危害效应,但内分泌评估却很少。因此,本研究旨在使用本地淡水鱼类 Astyanax lacustris 的雌性个体评估 DCF 和 IBU 单独和联合的破坏生理效应和毒性。关于 NSAIDs 的生物利用度,结果表明,IBU 和 DCF 在暴露 7 天后没有降解。A. lacustris 的 IBU LC 为 137 mg/L,单独暴露于 IBU 的雌性个体在 24 小时时增加甲状腺素 (T) 浓度,96 小时后降低;DCF 暴露在 96 小时时降低三碘甲状腺原氨酸 (T3) 浓度。循环中的 17β-雌二醇 (E)、皮质醇 (F) 和睾酮 (T) 水平不受任何处理的影响。HPG 和 HPI 轴基因 fshβ、pomc 和 vtg 在 IBU 暴露 24 小时后上调,而 Dio2 在 DCF 暴露组中 96 小时后下调。与混合物相比,DCF 和混合物暴露 24 小时后肌肉中的蛋白质浓度降低,肝脏中的蛋白质浓度增加;而混合物组在 96 小时后肝脏中的脂质增加。该研究表明 NSAIDs 有能力影响 A. lacustris 雌性个体的内分泌终点,并在单独和混合 NSAIDs 处理的急性暴露后诱导能量底物含量的变化。最后,本研究为 NSAIDs 在拉丁美洲鱼类和水生环境中的毒性和内分泌干扰活性提供了新的见解。