Protective role of metabolism by intestinal microflora in butyl paraben-induced toxicity in HepG2 cell cultures.
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.
Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
Tilak
T
Khanal
Hyung Gyun
HG
Kim
Sun Woo
SW
Jin
Eol
E
Shim
Hwa Jeong
HJ
Han
Keumhan
K
Noh
Sunkyoung
S
Park
Dae Hun
DH
Lee
Wonku
W
Kang
Hee Kyung
HK
Yeo
Dong Hyun
DH
Kim
Tae Cheon
TC
Jeong
Hye Gwang
HG
Jeong
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D005243:Feces / Q000382:microbiology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology*; D008297:Male; D010226:Parabens / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000873:Anthracenes; D010226:Parabens; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; C038091:butylparaben