title: Resveratrol inhibited hydroquinone-induced cytotoxicity in mouse primary hepatocytes.
abstract: Hydroquinone (1,4-benzenediol) has been widely used in clinical situations and the cosmetic industry because of its depigmenting effects. Most skin-lightening hydroquinone creams contain 4%-5% hydroquinone. We have investigated the role of resveratrol in prevention of hydroquinone induced cytotoxicity in mouse primary hepatocytes. We found that 400 µM hydroquinone exposure alone induced apoptosis of the cells and also resulted in a significant drop of cell viability compared with the control, and pretreatment of resveratrol to a final concentration of 0.5 mM 1 h before hydroquinone exposure did not show a significant improvement in the survival rate of the hepatocytes, however, relatively higher concentrations of resveratrol (≥1 mM) inhibited apoptosis of the mouse primary hepatocytes and increased cell viability in a dose-dependent manner, and in particular the survival rate of the hepatocytes was recovered from 28% to near 100% by 5 mM resveratrol. Interestingly, pretreatment with resveratrol for longer time (24 h), even in very low concentrations (50 µM, 100 µM), blocked the damage of hydroquinone to the cells. We also observed that resveratrol pretreatment suppressed hydroquinone-induced expression of cytochrome P450 2E1 mRNA dose-dependently. The present study suggests that resveratrol protected the cells against hydroquinone-induced toxicity through its antioxidant function and possibly suppressive effect on the expression of cytochrome P450 2E1.
authors.affiliation: Department of Public Health, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. dahong@md.okayama-u.ac.jp
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Wang
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Ootsuki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujita
authors.forename: Masahiro
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Qinxia
authors.initials: Q
authors.lastname: Yie
authors.forename: Ken
authors.initials: K
authors.lastname: Tsutsui
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Sano
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Masuoka
authors.forename: Keiki
authors.initials: K
authors.lastname: Ogino
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D006873:Hydroquinones / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013267:Stilbenes; D019392:Cytochrome P-450 CYP2E1; D000077185:Resveratrol; C031927:hydroquinone