Role of metabolism by the human intestinal microflora in arbutin-induced cytotoxicity in HepG2 cell cultures |
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Authors: | Khanal Tilak Kim Hyung Gyun Hwang Yong Pil Kong Min Jeong Kang Mi Jeong Yeo Hee Kyung Kim Dong Hyun Jeong Tae Cheon Jeong Hye Gwang |
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Institution: | aDepartment of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea;bCollege of Pharmacy, Yeungnam University, Gyeongsan 712-749, South Korea;cCollege of Pharmacy, Kyung Hee University, Seoul 130-701, South Korea;dDepartment of Food and Nutrition, Kyung Hee University, Seoul 130-701, South Korea |
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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. |
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Keywords: | Intestinal microflora Arbutin Hydroquinone Cytotoxicity Metabolism |
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