Inhibition of reactive oxygen species and pre-neoplastic lesions by quercetin through an antioxidant defense mechanism

Abstract

There is a correlation between oxidative stress generated by diethylnitrosamine (DEN) metabolism and liver cancer development. Quercetin is a flavonoid with anti-carcinogenic and antioxidant properties. This study demonstrates the mechanism of action for the chemopreventive effect of quercetin. A 10 mg/kg dose of quercetin produced drastic effect, when it is administrated 2 h before DEN; at 24 days post-DEN, a 70.3% and 66.2% decrease in total area and number of preneoplastic lesions were observed, respectively. At 12 h post-DEN, quercetin inhibited levels of lipid peroxidation by 40%. Quercetin increased the levels of both GSH and of total glutathione, it increased the GSH/GSSG index and it caused a rapid and simultaneous elevation in the activities of superoxide dismutase, glutathione peroxidase and catalase. In conclusion, the quercetin mechanism of action is due to promote the enzymatic and non-enzymatic antioxidant defense system during the initiation of hepatocarcinogenesis.

• Oxidative stress
• hepatocarcinogenesis
• antioxidant defense system
• chemoprevention
• quercetin

Abbreviations
HNE	=	4-hydroxy-2-nonenal
2-AAF	=	2-acetylaminofluorene
CAT	=	catalase
DEN	=	diethylnitrosamine
GGT	=	gamma-glutamyl-transpeptidase
GSSG	=	oxidized glutathione
GSH	=	reduced glutathione
GPx	=	glutathione peroxidase
GST	=	glutathione S-transferase
MDA	=	malondialdehyde
ROS	=	reactive oxygen species
SOD	=	superoxide dismutase

Abbreviations
HNE	=	4-hydroxy-2-nonenal
2-AAF	=	2-acetylaminofluorene
CAT	=	catalase
DEN	=	diethylnitrosamine
GGT	=	gamma-glutamyl-transpeptidase
GSSG	=	oxidized glutathione
GSH	=	reduced glutathione
GPx	=	glutathione peroxidase
GST	=	glutathione S-transferase
MDA	=	malondialdehyde
ROS	=	reactive oxygen species
SOD	=	superoxide dismutase