title: Involvement of intracellular glutathione in regulating isoline-induced cytotoxicity in human normal liver L-02 cells.
abstract: Pyrrolizidine alkaloid isoline is isolated from the traditional Chinese medicine Ligularia duciformis. Our previous reports have already demonstrated isoline-induced liver injury in mice. The present study is designed to observe the involvement of intracellular reduced glutathione (GSH) in isoline-induced cytotoxicity in human normal liver L-02 cells. The results showed that isoline decreased the cellular GSH and the ratio of GSH and oxidized glutathione in a time- and concentration-dependent manner in L-02 cells. l-Buthionine-S-R-sulfoximine (BSO) is reported to inhibit cellular GSH biosynthesis, and further results showed that isoline decreased the cell viability in L-02 cells after pretreated with 25 μM BSO for 24 h. Furthermore, adducts of isoline and GSH were identified in L-02 cells using liquid chromatography/electrospray ionization tandem mass spectrometry (ion trap) for the first time. In conclusion, our study provides the strongest evidence to support the important roles of GSH in regulating isoline-induced cytotoxicity in human normal liver L-02 cells.
authors.affiliation: The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Aizheng
authors.initials: A
authors.lastname: Xiong
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000704:Analysis of Variance; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002853:Chromatography, Liquid; D005978:Glutathione / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011763:Pyrrolizidine Alkaloids / Q000633:toxicity*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000975:Antioxidants; D011763:Pyrrolizidine Alkaloids; C489556:isoline; D005978:Glutathione