Resveratrol Inhibited Hydroquinone-Induced Cytotoxicity in Mouse Primary Hepatocytes

Da-Hong Wang,Hirofumi Fujita,Yoshie Ootsuki,Kuniaki Sano,Keiki Ogino,Ken Tsutsui,Qinxia Yie,Masahiro Miyazaki,Noriyoshi Masuoka

doi:10.3390/ijerph9093354

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.

Highlights

Hydroquinone (1,4-benzenediol, Figure 1), a benzene-derived metabolite, has been widely used in clinical situations and the cosmetics industry because of its depigmenting effect through its influence upon melanocyte metabolism [1,2]
Hydroquinone induced apoptosis was markedly decreased in the cells by resveratrol pretreatment (1 h before hydroquinone exposure), by 1 mM of resveratrol pretreatment
Our study proved that hydroquinone could cause apoptosis in mouse primary hepatocytes and pretreatment of resveratrol is capable of protect the cell against it

Summary

Introduction

Hydroquinone (1,4-benzenediol, Figure 1), a benzene-derived metabolite, has been widely used in clinical situations and the cosmetics industry because of its depigmenting effect through its influence upon melanocyte metabolism [1,2]. The U.S Food and Drug Administration (FDA) has reported that even low concentrations (1%–2%) of hydroquinone can cause exogenous ochronosis [4] and has proposed a ban on over-the-counter (OCT) hydroquinone. The European Committee has banned the use of hydroquinone in cosmetics in 2001 and only physicians and dermatologists can prescribe the hydroquinone formulations (24th Directive 2000/6/EC). Previous studies have demonstrated DNA damage induced by hydroquinone via generation of reactive oxygen species (ROS) [5,6,7,8,9], and hydroquinone-induced carcinogenicity was observed in both mice and rats [10].

Methods

Results

Conclusion