title: Role of metabolism by the human intestinal microflora in arbutin-induced cytotoxicity in HepG2 cell cultures.
abstract: A possible role for metabolism by the human intestinal microflora in arbutin-induced cytotoxicity was investigated using human hepatoma HepG2 cells. When the cytotoxic effects of arbutin and hydroquinone (HQ), a deglycosylated metabolite of arbutin, were compared, HQ was more toxic than arbutin. Incubation of arbutin with a human fecal preparation could produce HQ. Following incubation of arbutin with a human fecal preparation for metabolic activation, the reaction mixture was filter-sterilized to test its toxic effects on HepG2 cells. The mixture induced cytotoxicity in HepG2 cells in a concentration-dependent manner. In addition, the mixture considerably inhibited expression of Bcl-2 together with an increase in Bax expression. Likewise, activation stimulated cleavage of caspase-3 and production of reactive oxygen species in HepG2 cell cultures. Furthermore, induction of apoptosis by the intestinal microflora reaction mixture was confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end labeling assay. Taken together, these findings suggest that the human intestinal microflora is capable of metabolizing arbutin to HQ, which can induce apoptosis in mammalian cells.
authors: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
authors: Tilak
authors: T
authors: Khanal
authors: Hyung Gyun
authors: HG
authors: Kim
authors: Yong Pil
authors: YP
authors: Hwang
authors: Min Jeong
authors: MJ
authors: Kong
authors: Mi Jeong
authors: MJ
authors: Kang
authors: Hee Kyung
authors: HK
authors: Yeo
authors: Dong Hyun
authors: DH
authors: Kim
authors: Tae Cheon
authors: TC
authors: Jeong
authors: Hye Gwang
authors: HG
authors: Jeong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001104:Arbutin / Q000378:metabolism* / Q000494:pharmacology*; D001419:Bacteria / Q000378:metabolism*; D005243:Feces / Q000382:microbiology; D056945:Hep G2 Cells; D006801:Humans; D006873:Hydroquinones / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*
chemical_list: D006873:Hydroquinones; D001104:Arbutin; C031927:hydroquinone