TITLE:
Protective Effect of Resveratrol against Oxidation Stress Induced by 2-Nitropropane in Rat Liver
AUTHORS:
Maura Lodovici, Elisabetta Bigagli, Cristina Luceri, Elena M Manni, Mohamed Zaid
KEYWORDS:
2-nitropropane, 8-oxodGuo, lipoperoxidation, MDA, XO, SOD, resveratrol, apoptosis
JOURNAL NAME:
Pharmacology & Pharmacy,
Vol.2 No.3,
July
26,
2011
ABSTRACT: We investigated the effect of resveratrol on oxidation damage and variation of antioxidant defences induced by 2-nitropropane (2-NP) in rat liver. One group of five rats was given resveratrol (50 mg/kg/d body weight) in the diet until the end of the experiment. After 14 days, 2-NP (100 mg/kg) was injected i.p. into two groups of animals (2-NP + Res and 2-NP groups) while control animals were treated with vehicle alone. Animals were killed by decapitation 15 h after 2-NP injection. The levels of 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodGuo) were significantly increased by 2-NP injection, but resveratrol restored 8-oxodGuo to levels similar to those measured in controls. Superoxide dismutase (SOD) and xanthine oxidase (XO) activities in the liver were significantly increased by 2-NP, but were similar to those found in the group treated with resveratrol and 2-NP (2-NP + Res). We also observed that 2-NP injection significantly reduced GSH/GSSG ratio in the liver and this change was partially reversed by resveratrol treatment. Moreover, an increased (p = 0.06) expression of the oxoguanine glycosylase (OGG1) gene was found in 2-NP rats, whereas pre-treatment with resveratrol restored OGG1 expression to control levels. An up-regulation of caspase-3 was also observed in 2-NP group, but resveratrol significantly reduced the activation of caspase-3.
An inverse correlation was found between GSH/GSSG and 8-oxodGuo in the 2-NP group. On the contrary, 8-oxodGuo levels, GSH/GSSG ratio, XO and SOD activities in the colon mucosa of 2-NP rats were similar to those of controls confirming that the colon is not a target of oxidation damage 2-NP induced.
In conclusion, our results indicate that oxidative DNA damage and apoptosis are the main mechanisms of cell death in a model of chemically induced severe acute hepatic injury and in this early stage of damage pharmacological doses of resveratrol can ameliorate hepatic oxidation damage by its antioxidant and scavenging properties through a reduction of XO activity, a partial restoration of GSH/GSSG ratio in addition to its capacity to inhibit apoptosis.