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使用六个不同模型系统和十八个终点对卡马西平进行生态毒理学评估。

Ecotoxicological evaluation of carbamazepine using six different model systems with eighteen endpoints.

作者信息

Jos A, Repetto G, Rios J C, Hazen M J, Molero M L, del Peso A, Salguero M, Fernández-Freire P, Pérez-Martín J M, Cameán A

机构信息

National Institute of Toxicology, PO Box 863, 41080-Sevilla, Spain.

出版信息

Toxicol In Vitro. 2003 Oct-Dec;17(5-6):525-32. doi: 10.1016/s0887-2333(03)00119-x.

Abstract

The occurrence of pharmaceutically active compounds in the aquatic environment has been recognized as one of the emerging issues in environmental chemistry. However, the ecotoxicological effects of pharmaceuticals have still not been researched adequately. Carbamazepine, an anticonvulsant commonly present in surface and groundwater, was studied, using six ecotoxicological model systems with eighteen endpoints evaluated at different exposure time periods. The battery included the immobilization of Daphnia magna, bioluminescence inhibition in the bacterium Vibrio fischeri, growth inhibition of the alga Chlorella vulgaris, and micronuclei induction and root growth inhibition in the plant Allium cepa. Cell morphology, neutral red uptake, total protein content, MTS metabolization, lactate dehydrogenase leakage and activity and glucose-6-phosphate dehydrogenase activity were studied in the salmonid fish cell line RTG-2. The total protein content, LDH activity, neutral red uptake and MTT metabolization in Vero monkey kidney cells were also investigated. The most sensitive system to carbamazepine was the Vero cell line, followed by Chlorella vulgaris, Vibrio fischeri, Daphnia magna, Allium cepa, and RTG-2 cells. EC50 values from 19 microM in Vero cells at 72 h to more than 1200 microM in other systems, were obtained. Comparing the concentrations in water and the toxicity quantified in our assay systems, carbamazepine is not expected to produce acute toxic effects in the aquatic biota under these circumstances, but chronic and synergistic effects with other chemicals cannot be excluded.

摘要

药物活性化合物在水环境中的出现已被视为环境化学领域新出现的问题之一。然而,药物的生态毒理学效应仍未得到充分研究。对卡马西平(一种常见于地表水和地下水中的抗惊厥药)进行了研究,使用了六个生态毒理学模型系统,并在不同暴露时间段评估了十八个终点指标。该组实验包括大型溞的固定、费氏弧菌的生物发光抑制、普通小球藻的生长抑制,以及洋葱根尖细胞的微核诱导和根生长抑制。对鲑鱼细胞系RTG-2研究了细胞形态、中性红摄取、总蛋白含量、MTS代谢、乳酸脱氢酶泄漏及活性以及葡萄糖-6-磷酸脱氢酶活性。还研究了非洲绿猴肾细胞系Vero中的总蛋白含量、乳酸脱氢酶活性、中性红摄取和MTT代谢。对卡马西平最敏感的系统是Vero细胞系,其次是普通小球藻、费氏弧菌、大型溞、洋葱根尖细胞和RTG-2细胞。获得的半数效应浓度(EC50)值范围从72小时时Vero细胞中的19微摩尔到其他系统中超过1200微摩尔。比较水中的浓度和我们实验系统中量化的毒性,在这些情况下,预计卡马西平不会对水生生物群产生急性毒性作用,但不能排除其与其他化学物质产生的慢性和协同效应。

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