Protective role of metabolism by intestinal microflora in butyl paraben-induced toxicity in HepG2 cell cultures

Title
Protective role of metabolism by intestinal microflora in butyl paraben-induced toxicity in HepG2 cell cultures
Author(s)
Tilak Khanal[Tilak Khanal]김형균[김형균]진선우[진선우]심얼[심얼]한화정[한화정]노금한박선경이대훈강원구여희경[여희경]김동현[김동현]정태천정혜광[정혜광]
Keywords
BREAST-CANCER CELLS; HYDROXYBENZOIC ACID; HELA-CELLS; C-JUN; APOPTOSIS; P53; ESTERS; ACTIVATION; BACTERIA; ARBUTIN
Issue Date
201209
Publisher
ELSEVIER IRELAND LTD
Citation
TOXICOLOGY LETTERS, v.213, no.2, pp.174 - 183
Abstract
Parabens are alkyl esters of p-hydroxybenzoic acid (BA), including methyl paraben (MP), ethyl paraben, propyl paraben (PP), and butyl paraben (BP). In the present study, possible role of metabolism by fecalase in BP-induced cytotoxicity was investigated in HepG2 cell cultures. As an intestinal bacterial metabolic system, a human fecalase prepared from human fecal specimen was employed. Among the parabens tested, cytotoxicity of BP was most severe. BA, the de-esterified metabolite, did not induce cytotoxicity when compared to other parabens. When BP was incubated with fecalase, it rapidly disappeared, in association with reduced cytotoxicity in HepG2 cells. In addition, BP incubated with fecalase significantly caused an increase in Bcl-2 expression together with a decrease in Bax expression and cleaved caspase-3. Moreover, anti-apoptotic effect by the incubation of BP with fecalase was also confirmed by the TUNEL assay. Furthermore, BP induced a sustained activation of the phosphorylation of JNK only when it was treated alone. Meanwhile, BP-induced cell death was reversed by the pre-incubation of BP with either fecalase or SP600125. Taken together, the findings suggested that metabolism of BP by human fecalase might have protective effects against BP-induced toxicity in HepG2 cells. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/27351http://dx.doi.org/10.1016/j.toxlet.2012.07.004
ISSN
0378-4274
Appears in Collections:
중앙도서관 > rims journal
약학대학 > 약학부 > Articles
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