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杜罗河口(葡萄牙)发现的药物的毒性潜力:亚急性暴露后通过斑马鱼卵巢和睾丸的组织病理学和体视学研究评估对性腺成熟的影响。

The toxicity potential of pharmaceuticals found in the Douro River estuary (Portugal): assessing impacts on gonadal maturation with a histopathological and stereological study of zebrafish ovary and testis after sub-acute exposures.

机构信息

Superior Institute of Health Sciences - North (ISCS-N), CESPU, Gandra, Paredes, Portugal.

出版信息

Aquat Toxicol. 2011 Oct;105(3-4):292-9. doi: 10.1016/j.aquatox.2011.06.017. Epub 2011 Jun 28.

DOI:10.1016/j.aquatox.2011.06.017
PMID:21781654
Abstract

Concerns associated with pharmaceuticals in aquatic systems demand the establishment of links between xenobiotics and their respective concentrations and impacts on aquatic organisms. Herein, effects of non-steroidal pharmaceuticals in the gonadal maturation of zebrafish (Danio rerio) were evaluated by histopathological and stereological analyses after 21 days of exposure. Carbamazepine, fenofibric acid, propranolol, sulfamethoxazole and trimethoprim were selected, considering their detection in the Douro estuary (Portugal). Exposures were performed with single compounds and mixtures, the exposure concentrations including environmental levels. Overall, quantitative analyses showed a decreasing trend for late maturation stages in male and female gametogenesis with parallel increases in immature gametes. In females, and at the highest concentration mixture, a significant switch between the volume densities of late/mature oocytes versus primary oocytes was observed. On the verge of statistical significance, oocyte atresia was higher in both mixtures (5.75 ± 4.02% for MXA and 5.65 ± 5.27% for MXB) versus control (2.21 ± 1.88%), in accordance with the histological identification of large atretic areas in some fish. Unlike females, males showed significant effects with single exposures. Spermatozoa in controls totalled 53.25 ± 7.13% of the testis volume, decreasing with carbamazepine (47.19 ± 5.30%), fenofibric acid (46.36 ± 4.30%), propranolol (37.22 ± 2.38%) and sulfametoxazole (39.37 ± 5.15%). An increase in spermatocyte percentage was noted with propranolol (40.13 ± 7.36%) and sulfametoxazole (40.84 ± 1.66%) versus control (30.93 ± 6.53%). The changes in maturation dynamics did not impact the gonadosomatic index. The results show that pharmaceuticals from various therapeutic classes can disrupt the maturation dynamics of fish ovaries and testes. Further studies are justified to tackle the underlying mechanisms and to gauge the full extent of effects/risks.

摘要

水生系统中药物相关问题促使人们建立污染物与其在水生生物体内的浓度和影响之间的联系。本研究通过组织病理学和体视学分析,评估了 21 天暴露于非甾体类药物后斑马鱼(Danio rerio)的性腺成熟情况。选择卡马西平、非诺贝特酸、普萘洛尔、磺胺甲噁唑和甲氧苄啶,是因为它们在葡萄牙杜罗河口被检测到。采用单一化合物和混合物进行暴露,暴露浓度包括环境水平。总体而言,雄性和雌性配子发生的晚期成熟阶段的定量分析显示出下降趋势,同时不成熟配子的数量增加。在雌性中,在最高浓度混合物中,观察到晚期/成熟卵母细胞与初级卵母细胞的体积密度之间的显著转变。在统计上有意义的边缘,两种混合物(MXA 为 5.75±4.02%,MXB 为 5.65±5.27%)中的卵母细胞退化率明显高于对照组(2.21±1.88%),这与一些鱼类中发现的大退化区域的组织学鉴定一致。与雌性不同,雄性的单一暴露也表现出显著影响。对照组睾丸中的精子总数为睾丸体积的 53.25±7.13%,卡马西平(47.19±5.30%)、非诺贝特酸(46.36±4.30%)、普萘洛尔(37.22±2.38%)和磺胺甲噁唑(39.37±5.15%)使精子总数减少。与对照组(30.93±6.53%)相比,普萘洛尔(40.13±7.36%)和磺胺甲噁唑(40.84±1.66%)中精母细胞的百分比增加。成熟动力学的变化并未影响性腺指数。结果表明,来自不同治疗类别的药物可破坏鱼类卵巢和睾丸的成熟动力学。有理由进行进一步研究,以探讨潜在机制并评估影响/风险的全部范围。

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