基于组合指数法评估抗生素二元混合物对青海弧菌Q67的时间依赖联合毒性
Assessment of Time-dependent Combined Toxicity of Antibiotic Binary Mixtures to Vibrio qinghaiensis sp.-Q67 Based on Combination Index Method
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摘要: 污染物在环境混合暴露是一种普遍现象。然而，目前对污染物时间毒性及相互作用大多只考虑了相互作用类型，缺乏对于相互作用大小及出现频率的研究。因此，本研究以水环境中普遍存在的3种不同类别抗生素恩诺沙星(enrofloxacin, ENR)、氯霉素(chloramphenicols, CMP)和红霉素(erythromycin, ETM)为目标污染物，以青海弧菌Q67为指示生物，运用直接均分射线法(equipartition ray, EquRay)设计3个二元混合体系共15条混合物射线，应用时间依赖微板毒性分析法测定了3种抗生素及其二元混合物的时间-浓度-效应数据，并采用组合指数(combination index, CI)分析混合物的毒性作用随暴露时间变化趋势，并分析加和、协同和拮抗3种相互作用出现的频率，探究抗生素混合物毒性相互作用变化规律。结果表明，随暴露时间的延长，3种抗生素对Q67的毒性逐渐增强，ENR暴露在8～12 h时，对Q67存在明显的Hormesis，最大刺激效应为-102.12%。所有的二元混合物都呈现明显的时间毒性，且高浓度区域时间毒性变化较为明显，不同于单一毒性，15条混合射线均未出现Hormesis。抗生素混合物毒性相互作用类型及作用程度与组分浓度比、浓度大小及暴露时间均有关，其中暴露浓度影响最大。通过利用混合物相互作用在指定效应下的出现频率分析，在这3种混合体系中，加和作用出现的频率最高，拮抗作用出现的频率最低，混合物暴露在低浓度区域多呈加和作用，高浓度区域多呈协同作用。Abstract: Mixed exposure to pollutants in the environment is a common phenomenon. However, most of the current studies focusing on the temporal toxicity and interactions of various contaminants have only considered the types of interaction, and studies on the magnitudes and frequencies of their interactions are still lacking. Therefore, three different antibiotics classes including enrofloxacin (ENR), chloramphenicol (CMP), and erythromycin (ETM) were selected in this study as target contaminants, due to the fact that these compounds are commonly observed in the aqueous environment. Vibrio qinghaiensis sp.-Q67 (Q67 was used below) was used as an indicator organism, and a total of 15 mixture rays were designed based on the three binary mixture systems using the direct equipartition ray (EquRay). The time-dependent microplate toxicity analysis was also applied to determine the time-concentration-effect data of the three antibiotics. Furthermore, their binary mixtures were measured by time-dependent microplate toxicity analysis, and the trends of the toxic effects of these mixtures with exposure times were analyzed by using the combination index (CI). In addition, the frequencies of the three interactions including additive action, synergism, and antagonism were analyzed to investigate the change laws of the toxic interactions of the antibiotic mixtures. The results showed that the toxicity of the three antibiotics on Q67 gradually increased with the extension of the exposure time, and there was a significant Hormesis on Q67 at times of 8 h and 12 h of ENR exposure, with the maximum stimulation point of -102.12%. The binary mixtures results showed significant temporal toxicity, and the changes of temporal toxicity were more obvious at high concentrations. This result was different with that observed in the toxicity of single compounds, while no Hormesis was observed for any of the 15 mixed rays. Significant correlations were observed among the types of antibiotic mixture toxic interactions and the degree of action, and the component concentration ratio, concentration size, and exposure time. Among them, exposure concentration showed the greatest effect. The frequencies of the occurrence of mixture interactions at the specified effect were analyzed. In the three mixed systems, the highest frequency of additive interactions and the lowest frequency of antagonistic interactions were all observed, while the mixture systems showed more additive interactions at the low concentration and more synergistic interactions at the high concentration.
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Key words:
- enrofloxacin /
- chloramphenicol /
- erythromycin /
- Vibrio qinghaiensis sp.-Q67 /
- combined toxicity /
- interaction
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