School of Biotechnology, Dublin City University, D09 Y5NO Dublin, Ireland.
Department of Molecular Systems Biology, Helmholtz-Centre for Environmental Research-UFZ, 04318 Leipzig, Germany.
Int J Mol Sci. 2023 Feb 17;24(4):4100. doi: 10.3390/ijms24044100.
Pharmaceutical compounds are among several classes of contaminants of emerging concern, such as pesticides, heavy metals and personal care products, all of which are a major concern for aquatic ecosystems. The hazards posed by the presence of pharmaceutical is one which affects both freshwater organisms and human health-via non-target effects and by the contamination of drinking water sources. The molecular and phenotypic alterations of five pharmaceuticals which are commonly present in the aquatic environment were explored in daphnids under chronic exposures. Markers of physiology such as enzyme activities were combined with metabolic perturbations to assess the impact of metformin, diclofenac, gabapentin, carbamazepine and gemfibrozil on daphnids. Enzyme activity of markers of physiology included phosphatases, lipase, peptidase, β-galactosidase, lactate dehydrogenase, glutathione-S-transferase and glutathione reductase activities. Furthermore, targeted LC-MS/MS analysis focusing on glycolysis, the pentose phosphate pathway and the TCA cycle intermediates was performed to assess metabolic alterations. Exposure to pharmaceuticals resulted in the changes in activity for several enzymes of metabolism and the detoxification enzyme glutathione-S-transferase. Metabolic perturbations on key pathways revealed distinct groups and metabolic fingerprints for the different exposures and their mixtures. Chronic exposure to pharmaceuticals at low concentrations revealed significant alterations of metabolic and physiological endpoints.
药物化合物是几种新兴关注污染物类别之一，如农药、重金属和个人护理产品，所有这些都对水生生态系统构成了重大威胁。药物存在带来的危害既影响到淡水生物，也影响到人类健康——通过非靶标效应和饮用水源的污染。在慢性暴露下，对水生环境中常见的五种药物进行了研究，探讨了它们对水蚤的分子和表型改变。将生理标志物如酶活性与代谢扰动结合起来，评估了二甲双胍、双氯芬酸、加巴喷丁、卡马西平和吉非贝齐对水蚤的影响。生理标志物的酶活性包括磷酸酶、脂肪酶、肽酶、β-半乳糖苷酶、乳酸脱氢酶、谷胱甘肽-S-转移酶和谷胱甘肽还原酶活性。此外，还进行了靶向 LC-MS/MS 分析，重点关注糖酵解、磷酸戊糖途径和 TCA 循环中间产物，以评估代谢变化。药物暴露导致几种代谢酶和解毒酶谷胱甘肽-S-转移酶的活性发生变化。关键途径上的代谢扰动揭示了不同暴露及其混合物的不同分组和代谢特征。在低浓度下的慢性药物暴露会导致代谢和生理终点的显著改变。
