Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233 Gdańsk, Poland.
Department of Analytical Chemistry, Faculty of Chemistry, Gdańsk University of Technology, 11/12 Narutowicza Str., 80-233 Gdańsk, Poland.
Environ Pollut. 2018 Jun;237:549-558. doi: 10.1016/j.envpol.2018.02.084. Epub 2018 Mar 15.
Assessment of the impact of pharmaceutical residues on living organisms is a very complex subject. Apart from taking into account the toxicity of individual compounds, environmental factors should also be taken into account. In this paper, attempts were made to assess the impact of coexisting inorganic ions and changes in pH on the toxicity of ten selected pharmaceuticals. Two bioassays were used to measure the estrogenic and androgenic effects (XenoScreen YES/YAS - Saccharomyces cerevisiae) and acute toxicity (Microtox - Vibrio fischeri). The Microtox test gave the most definitive outputs concerning the determination of interaction type between drugs and chemical species. Synergism was proven for almost all drugs and chemical species, and only two cases of antagonism were found. Significant drug/pH interactions were rare. Regarding the XenoScreen YES/YAS bioassay, when estrogenic and androgenic agonistic effects (YES+ and YAS+, respectively) were studied, many cases of well-expressed synergism for all inorganic ions with limited number of drugs (diazepam, fluoxetine, estrone, chloramphenicol for the YES+ test and diazepam, progesterone, androstenedione, and estrone for the YAS+ test) were found. Antagonism was also proven for the YES+ test, especially for diclofenac and androstenedione interacting with cations. On the other hand, the YES- and YAS- tests (estrogenic and androgenic, respectively, antagonistic effects) did not indicate cases of synergetic interaction except for the couples Br/diazepam and NH/ketoprofen. Antagonistic drug/ion interactions were detected only with diclofenac and fluoxetine. It is interesting that well-expressed (antagonism or synergism) drug/pH interactions were rare. Both tests were found utilizable in performing studies on impact of ions/pH fluctuations on drugs mixtures' toxicity confirming in most cases synergic impact of parameters studied on toxicity. The approach proposed in the paper seems to be proven as a reliable tool in assessing impact of abiotic factors on toxicity and endocrine potential of complex mixtures of pharmaceuticals' mixtures.
评估药物残留对生物的影响是一个非常复杂的课题。除了要考虑到单个化合物的毒性，还应考虑环境因素。在本文中，尝试评估共存无机离子和 pH 值变化对十种选定药物毒性的影响。使用两种生物测定法来测量雌激素和雄激素效应（XenoScreen YES/YAS-Saccharomyces cerevisiae）和急性毒性（Microtox-Vibrio fischeri）。Microtox 试验在确定药物与化学物质之间的相互作用类型方面给出了最明确的结果。几乎所有的药物和化学物质都被证明具有协同作用，只有两种拮抗作用的情况。药物与 pH 值之间的显著相互作用很少见。对于 XenoScreen YES/YAS 生物测定法，当研究雌激素和雄激素激动效应（分别为 YES+和 YAS+）时，对于所有无机离子与有限数量的药物（地西泮、氟西汀、雌酮、氯霉素用于 YES+测试和地西泮、孕酮、雄烯二酮和雌酮用于 YAS+测试），发现了许多表达良好的协同作用的情况。对于 YES+测试，还证明了拮抗作用，尤其是对于与阳离子相互作用的双氯芬酸和雄烯二酮。另一方面，YES-和 YAS-测试（分别为雌激素和雄激素，拮抗效应）除了 Br/地西泮和 NH/酮洛芬外，没有显示出协同相互作用的情况。仅检测到与双氯芬酸和氟西汀的拮抗药物/离子相互作用。有趣的是，表达良好的（拮抗或协同）药物/pH 值相互作用很少见。这两种测试都被发现可用于研究离子/pH 值波动对药物混合物毒性的影响，证实了在所研究的参数对毒性的协同影响在大多数情况下是合理的。本文提出的方法似乎已被证明是评估非生物因素对复杂药物混合物毒性和内分泌潜力的可靠工具。
