Esculetin-induced protection of human hepatoma HepG2 cells against hydrogen peroxide is associated with the Nrf2-dependent induction of the NAD(P)H: Quinone oxidoreductase 1 gene

Journal Article · Sat Jan 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.09.025· OSTI ID:21535210

Subramaniam, Sudhakar R

Esculetin (6,7-dihydroxy coumarin), is a potent antioxidant that is present in several plant species. The aim of this study was to investigate the mechanism of protection of esculetin in human hepatoma HepG2 cells against reactive oxygen species (ROS) induced by hydrogen peroxide. Cell viability, cell integrity, intracellular glutathione levels, generation of reactive oxygen species and expression of antioxidant enzymes were used as markers to measure cellular oxidative stress and response to ROS. The protective effect of esculetin was compared to a well-characterized chemoprotective compound quercetin. Pre-treatment of HepG2 cells with sub-lethal (10-25 {mu}M) esculetin for 8 h prevented cell death and maintained cell integrity following exposure to 0.9 mM hydrogen peroxide. An increase in the generation of ROS following hydrogen peroxide treatment was significantly attenuated by 8 h pre-treatment with esculetin. In addition, esculetin ameliorated the decrease in intracellular glutathione caused by hydrogen peroxide exposure. Moreover, treatment with 25 {mu}M esculetin for 8 h increased the expression of NAD(P)H: quinone oxidoreductase (NQO1) at both protein and mRNA levels significantly, by 12-fold and 15-fold, respectively. Esculetin treatment also increased nuclear accumulation of Nrf2 by 8-fold indicating that increased NQO1 expression is Nrf2-mediated. These results indicate that esculetin protects human hepatoma HepG2 cells from hydrogen peroxide induced oxidative injury and that this protection is provided through the induction of protective enzymes as part of an adaptive response mediated by Nrf2 nuclear accumulation.

• OSTI ID: 21535210
• Journal Information: Toxicology and Applied Pharmacology, Vol. 250, Issue 2; Other Information: DOI: 10.1016/j.taap.2010.09.025; PII: S0041-008X(10)00367-4; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIOXIDANTS
BENZOQUINONES
DPPH
GLUTATHIONE
HEPATOMAS
HYDROGEN PEROXIDE
LACTATE DEHYDROGENASE
SAFETY
VIABILITY
AROMATICS
CARCINOMAS
DISEASES
DRUGS
ENZYMES
HEMIACETAL DEHYDROGENASES
HYDROGEN COMPOUNDS
NEOPLASMS
NITRO COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
OXIDOREDUCTASES
OXYGEN COMPOUNDS
PEPTIDES
PEROXIDES
POLYPEPTIDES
PROTEINS
QUINONES
RADICALS
RADIOPROTECTIVE SUBSTANCES
RESPONSE MODIFYING FACTORS