Application of lipid peroxidation products as biomarkers for flutamide-induced oxidative stress in vitro
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- 作者：Marieke Teppnera ; b ; 1 ; marieke.teppner@evotec.com" class="auth_mail" title="E-mail the corresponding author ; Franziska Bö ; ssa ; Beat Ernstb ; Axel Pä ; hlera ; axel.paehler@roche.com" class="auth_mail" title="E-mail the corresponding author
- 关键词：15R-PD2 ; 15R-prostaglandin D2 ; DHN-MA ; 1 ; 4-dihydroxynonene mercapturic acid ; Dihydro-keto PE2 ; 13 ; 14-dihydro-15-keto prostaglandin E2 ; DILI ; drug-induced liver injury ; HNE ; 4-hydroxy-2(E)-nonenal ; HNE-MA ; HNE mercapturic acid ; HRP ; horseradish peroxidase ; iPF2α-VI ; 5-iso prostaglandin F2α-VI ; LDH ; lactate dehydrogenase ; PE2 ; prostaglandin E2 ; ROS ; reactive oxygen species
- 刊名：Toxicology Letters
- 出版年：2015
- 出版时间：4 November 2015
- 年：2015
- 卷：238
- 期：3
- 页码：53-59
- 全文大小：1072 K
文摘
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This paper describes the increase of isoprostanes and hydroxynonenal (HNE) derivatives as early safety biomarkers of hepatotoxicity caused by oxidative stress.
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The hepatotoxic drug flutamide provoked oxidative stress in primary hepatocytes resulting in a time and dose dependent increase of 15R-prostaglandin D2, prostaglandin E2, 13,14-dihydro-15-keto prostaglandin E2 and 5-iso prostaglandin F2α VI.
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HNE-mercapturic acid and its metabolite dihydroxynonene-mercapturic acid were also time and concentration dependently increased.
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Lipid peroxidation products as markers of reactive oxygen species were demonstrated to be more sensitive than conventional cytotoxicity markers for an early detection of drug-induced liver injury.