Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, Trav.14, n° 321, 05508-090 São Paulo, SP, Brazil.
Universidade Anhembi-Morumbi, Campus Mooca, São Paulo, SP, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2020 May;231:108720. doi: 10.1016/j.cbpc.2020.108720. Epub 2020 Jan 28.
Diclofenac (DCF) and caffeine (CAF) are persistent pharmaceuticals that occur in mixtures in the aquatic ecosystems causing effects in the reproductive physiology of aquatic organisms. This study evaluated the physiological reproductive responses of Astyanax altiparanae males exposed to nominal concentrations of DCF (3.08 mg L) and CAF (9.59 mg L) separately and combined, for 96 h. The steroids profile, estrogenic biomarker vitellogenin (vtgA), testes and liver morphology, and also mortality of males were assessed. DCF and CAF degradation was 5% of the initial concentration for 24 h. The LC of the DCF and CAF were 30.8 mg L and 95.9 mg L, respectively. Males exposed to DCF and CAF exhibited a reduction of 17β-Estradiol (E) concentration compared to control (CTL). Similarly, testosterone (T) was also reduced in the DCF treatment, but this response was not observed in 11-Ketotestosterone (11-KT). Males exposed to DCF + CAF combined did not exhibit differences in T, E and 11-KT steroids. The vtgA gene expression and the sperm concentration did not change among the treatments. Moreover, acute exposure revealed a hypertrophy of hepatocytes cells in the DCF and DCF + CAF treatments. In conclusion, DCF and CAF, isolated, exhibit an endocrine disruptive activity in A. altiparanae male, an opposite response observed with the mixture of both compounds that abolishes the endocrine disruptive effects. DCF seems to be more toxic for this species, altering also hepatocytes morphology.
双氯芬酸 (DCF) 和咖啡因 (CAF) 是持久性药物,它们在水生生态系统中以混合物的形式存在,对水生生物的生殖生理产生影响。本研究评估了暴露于标称浓度的 DCF(3.08 mg L)和 CAF(9.59 mg L)的虹鳉雄性个体的生理生殖反应,分别和联合暴露 96 h。评估了类固醇谱、雌激素生物标志物卵黄蛋白原 (vtgA)、睾丸和肝脏形态以及雄性个体的死亡率。暴露于 24 h 时,DCF 和 CAF 的降解率分别为初始浓度的 5%。LC50 分别为 30.8 和 95.9 mg L。与对照组(CTL)相比,暴露于 DCF 和 CAF 的雄性个体 17β-雌二醇 (E) 浓度降低。同样,在 DCF 处理中,睾酮 (T) 也减少,但在 11-酮睾酮 (11-KT) 中未观察到这种反应。暴露于 DCF + CAF 混合物的雄性个体在 T、E 和 11-KT 类固醇方面没有差异。vtgA 基因表达和精子浓度在处理组之间没有变化。此外,急性暴露导致 DCF 和 DCF + CAF 处理中的肝细胞细胞肥大。总之,DCF 和 CAF 单独暴露会对虹鳉雄性个体产生内分泌干扰活性,而混合两种化合物则会产生相反的反应,从而消除内分泌干扰作用。DCF 对该物种似乎更具毒性,还改变了肝细胞的形态。