title: Intracellular glutathione plays important roles in pyrrolizidine alkaloids-induced growth inhibition on hepatocytes.
abstract: Pyrrolizidine alkaloids (PAs) are well-known natural hepatotoxins distributed widely in thousands of plants in the world. Adonifoline (Adon), senecionine (Sene) and monocrotaline (Mono) are retronecine-type PAs, and the present study is designed to observe the effects of intracellular glutathione on toxicity of these three PAs in human normal liver L-02 cells. The ratio of cellular reduced glutathione (GSH) and oxidized glutathione (GSSG) was assayed after L-02 cells were incubated with these three PAs for various times. Results showed that Adon, Sene and Mono all significantly decreased the ratio of GSH/GSSG in L-02 cells in the time- and concentration-dependent manner. The results of 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and trypan blue staining assay showed that these three PAs all significantly decreased cell viability in L-02 cells when pretreated with 10μM BSO (L-Buthionine-S-R-Sulfoximine) for 24h to deplete intracellular GSH. Further results showed that anti-oxidant compounds such as NAC (N-Acetyl-Cysteine) and GSH could rescue the cytotoxicity caused by these three PAs with BSO pretreatment. Taken together, those results suggest that intracellular GSH plays important roles in regulating the cytotoxicity induced by PAs.
authors.affiliation: Department of Pharmacognosy, China Pharmaceutical University, Nanjing, 210038, PR China; Key Laboratory of Standardization of Chinese Medicines of Ministry of Education, Shanghai Key Laboratory of Complex Prescription, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Lili
authors.initials: L
authors.lastname: Ji
authors.forename: Haitao
authors.initials: H
authors.lastname: Wang
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Wang