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Regulation of endogenic metabolites by rosuvastatin in hyperlipidemia patients: An integration of metabolomics and lipidomics

Title
Regulation of endogenic metabolites by rosuvastatin in hyperlipidemia patients: An integration of metabolomics and lipidomics
Authors
Lee H.Choi J.M.Cho J.-Y.Kim T.-E.Lee H.J.Jung B.H.
Ewha Authors
이화정
SCOPUS Author ID
이화정scopus
Issue Date
2018
Journal Title
Chemistry and Physics of Lipids
ISSN
0009-3084JCR Link
Citation
Chemistry and Physics of Lipids vol. 214, pp. 69 - 83
Keywords
HyperlipidemiaLipidomicsMetabolomicsRosuvastatinStatin-induced myopathy
Publisher
Elsevier Ireland Ltd
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Rosuvastatin is a statin used to treat metabolic syndrome conditions, such as hyperlipidemia. It is relatively safe; however, fatal rhabdomyolysis or skeletal myopathy can sometimes occur. Therefore, to investigate the overall effects of rosuvastatin, including lipid lowering and adverse effects, metabolic profiling was performed using metabolomics and lipidomics after rosuvastatin administration. Specifically, the metabolic profiles between healthy subjects and patients with hyperlipidemia were compared and the metabolic changes related to the mechanism of the drug effect were proposed. Healthy volunteers (n = 32) and hyperlipidemic patients (n = 14) were orally administered rosuvastatin (20 mg) once a day for 3–8 weeks, and plasma and urine were collected. Metabolomics and lipidomics were performed using UHPLC-LTQ/Orbitrap/MS/MS for non-targeted analysis and UHPLC-TQ-MS/MS for targeted analysis. Using non-targeted analysis, we successfully profiled and identified 73 and 87 metabolites in healthy subjects and hyperlipidemia subjects, respectively. Through targeted analysis, we have also quantified 188 metabolites, including amino acids, biogenic amines, glycerophospholipids, and sphingolipids. The levels of L-carnitine, diacylglycerol, and acylcarnitines significantly decreased after rosuvastatin administration regardless of the group. The overall levels of fatty acids (FA) and lysophosphatidylcholines (LysoPC) increased, while phosphatidylcholines (PC) decreased only in the patient group. β-Oxidation decreased overall, while the production of polyunsaturated FA increased only in the hyperlipidemic patients. Using metabolic profiling, we have evaluated the alterations in the biochemical pathways, which may aid in a more detailed understanding of the effect of rosuvastatin. Patient-specific metabolomic and lipidomic profiles may serve as valuable markers for the understanding of the adverse effects associated with statin treatment. © 2018 Elsevier B.V.
DOI
10.1016/j.chemphyslip.2018.05.005
Appears in Collections:
약학대학 > 약학과 > Journal papers
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