잉어의 생체 내 대사체 변화에 미치는 플록세틴 영향규명 연구
A Study of the Adverse Effects of Fluoxetine on Cyprinus carpio Metabolomics
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
The purpose of this study was to clarify the effect of fluoxetine, one of the most frequently prescribed antidepressant drugs, on Cyprinus carpio by comparing the variations in its metabolite concentrations after exposure to the drug, using NMR and LC/Orbitrap MS. Three experimental reactors were employed, and the total experimental period was 14 days. Cyprinus carpio were acclimatized for 3 months in the laboratory and then subjected to the study. One reactor was used as a 14-day control, and the others were exposed to fluoxetine at 10 ng/L and 10 μg/L for 7 days and depurate for 7 days. The variations in metabolite concentration after exposure were analyzed by NMR and LC/Orbitrap MS. Before exposure, the concentration trends of fluoxetine and its main metabolite, norfluoxetine were almost the same in blood and liver samples of Cyprinus carpio. However, after the depuration period, the concentrations of norfluoxetine in the liver and blood samples were higher than those of fluoxetine. The concentration of the remaining norfluoxetine in the liver sample was higher than that in the blood sample. This means that the liver mainly metabolized pharmaceuticals. The main change in the concentrations of metabolites of Cyprinus carpio was shown in amino acids such as leucine, isoleucine, glutamate, tyrosine, and valine; organic acids such as acetate and formate; creatine; and glucose. Although after the depuration period, the control, and 10 ng/L and 10 μg/L exposure groups had overlapping results, the exposure and control groups could be classified clearly after 14 days. These results are expected to contribute to identifying the effects of environmental pollutants by tracing metabolite changes and building a chemical metabolite database
Abstract
The purpose of this study was to clarify the effect of fluoxetine, one of the most frequently prescribed antidepressant drugs, on Cyprinus carpio by comparing the variations in its metabolite concentrations after exposure to the drug, using NMR and LC/Orbitrap MS. Three experimental reactors were employed, and the total experimental period was 14 days. Cyprinus carpio were acclimatized for 3 months in the laboratory and then subjected to the study. One reactor was used as a 14-day control, and the others were exposed to fluoxetine at 10 ng/L and 10 μg/L for 7 days and depurate for 7 days. The variations in metabolite concentration after exposure were analyzed by NMR and LC/Orbitrap MS. Before exposure, the concentration trends of fluoxetine and its main metabolite, norfluoxetine were almost the same in blood and liver samples of Cyprinus carpio. However, after the depuration period, the concentrations of norfluoxetine in the liver and blood samples were higher than those of fluoxetine. The concentration of the remaining norfluoxetine in the liver sample was higher than that in the blood sample. This means that the liver mainly metabolized pharmaceuticals. The main change in the concentrations of metabolites of Cyprinus carpio was shown in amino acids such as leucine, isoleucine, glutamate, tyrosine, and valine; organic acids such as acetate and formate; creatine; and glucose. Although after the depuration period, the control, and 10 ng/L and 10 μg/L exposure groups had overlapping results, the exposure and control groups could be classified clearly after 14 days. These results are expected to contribute to identifying the effects of environmental pollutants by tracing metabolite changes and building a chemical metabolite database
참고문헌 (20)
- C. Fernández, "Occurrence of pharmaceutically active compounds in surface waters of the henares-jarama-tajo river system(madrid, spain) and a potential risk characterization", Science of the Total Environment, 408, pp.543~551 (2010)
- A. R. R. Péry, "Fluoxetine effects assessment on the life cycle of aquatic invertebrates", Chemosphere, 73, pp.300~304 (2008)
- Lúcia H. M. L. M. Santos, "Contributions of hospital effluents to the load of pharmaceuticals in urban wastewaters:Identification of ecologically relevant pharmaceuticals", Science of the Total Environment, 461-462, pp.302~316 (2013)
- Y. Nakamura, "The effects of pH on fluoxetine in Japanese medaka(Oryzias latipes): Acute toxicity in fish larvae and bioaccumulation in juvenile fish", Chemosphere, 70, pp.865~873 (2008)
- 잔류 의약물질 환경위해성 평가(Ⅰ), "국립환경과학원", 137~139 (2008)
- V. K. H. Barclay, "Trace analysis of fluoxetine and its metabolite norfluoxetine. Part II: Enantioselective quantification and studies of matrix effects in raw and treated wastewater by solid phase extraction and liquid chromatography-tandem mass spectrometry", Journal of Chromatography A, 1227, pp.105~114 (2012)
- B. W. Brooks, "Aquatic ecotoxicology of fluoxetine", Toxicology Letters, 142, pp.169~183 (2003)
- R. Lazzara, "Low environmental levels of fluoxetine induce spawning and changes in endogenous estradiol levels in the zebra mussel Dreissena polymorpha", Aquatic Toxicology, 106-107, pp.123~130 (2012)
- V. K. H. Barclay, "Trace analysis of fluoxetine and its metabolite norfluoxetine. Part I: Development of a chiral liquid chromatography-tandem mass spectrometry method for wastewater samples", Journal of Chromatography A, 1218, pp.5587~5596 (2011)
- M. M. Schultz, "Trace Analysis of Antidepressant Pharmaceuticals and their select degradates in aquatic matrixes by LC", ESI, MS, pp.Analytical Chemistry, 2008[DOI]
- S. Chu, "Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry", Journal of Chromatography A, 1163, pp.112~118 (2007)
- 손보영, "LC-MS", MS를 이용한 베타락탐계 항생제와 베타차단제의 동시분석, 2016, pp.29(4), 179~185[DOI]
- V. Contrusciere, "Branched-chain amino acids induce neurotoxicity in rat cortical cultures", Neurotoxicity Research, 17, pp.392~398 (2010)
- L. E. Banderet, "Treatment with tyrosine, a neurotransmitter precursor, reduces environmental stress in humans", Brain Research Bulletin, 22, pp.759~762 (1989)
- J. Zeng, "Effect of bisphenol A on rat metabolic profiling studied by using capillary electrophoresis time-of-flight mass spectrometry", Environmental Science & Technology, 47, pp.7457~7465 (2013)
- F. Carvalho, "Hyperglycemia induced by acute central fluoxetine administration:role of the central CRH system and 5-HT3receptors", Neuropeptide, 38, pp.98~105 (2004)
- K. Nonogaki, "Role of central neural mechanism in the regulation of hepatic glucose metabolism", Life Science, 60, pp.797~807 (1997)
- E. W. Boyer, "The serotonin syndrome", The New England Journal of Medicine, 352, pp.1112~1120 (2005)
- P. Thulin, "PPARα regulates the hepatotoxic biomarker alanine aminotransferase (ALT1) gene expression in human hepatocytes", Toxicology and Applied Pharmacology, 231, pp.1~9 (2008)
- M. Erecin’ska, "Neurotransmitter amino acids in the CNS. I. regional changes in amino acid levels in rat brain during ischemia and reperfusion", Brain Research, 304, pp.9~22 (1984)