Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice.

Abstract

Olives and olive products, an inevitable part of the Mediterranean diet, possess various beneficial effects, such as a decreased risk of cardiovascular disease and cancer. Oleuropein is a non-toxic secoiridoid found in the leaves and fruits of olive (Olea europaea L.). In this study, we have investigated the hepatoprotective activity of oleuropein in carbon tetrachloride (CCl(4))-induced liver injury in male BALB/cN mice. Oleuropein in doses of 100 and 200mg/kg was administered intraperitoneally (ip) once daily for 3 consecutive days, prior to CCl(4) administration (the preventive treatment), or once daily for 2 consecutive days 6h after CCl(4) intoxication (the curative treatment). CCl(4) intoxication resulted in a massive hepatic necrosis and increased plasma transaminases. Liver injury was associated with oxidative/nitrosative stress evidenced by increased nitrotyrosine formation as well as a significant decrease in superoxide dismutase activity and glutathione levels. CCl(4) administration triggered inflammatory response in mice livers by inducing expression of nuclear factor-kappaB, which coincided with the induction of tumor necrosis factor-alpha, cyclooxygenase-2 and inducible nitric oxide synthase. In both treatment protocols, oleuropein significantly attenuated oxidative/nitrosative stress and inflammatory response and improved histological and plasma markers of liver damage. Additionally, in the curative regimen, oleuropein prevented tumor necrosis factor-beta1-mediated activation of hepatic stellate cells, as well as the activation of caspase-3. The hepatoprotective activity of oleuropein was, at least in part, achieved through the NF-E2-related factor 2-mediated induction of heme oxygenase-1. The present study demonstrates antioxidant, anti-inflammatory, antiapoptotic, and antifibrotic activity of oleuropein, with more pronounced therapeutic than prophylactic effects.

• Authors: Robert Domitrović, Hrvoje Jakovac, Vanja Vasiljev Marchesi, Ivana Šain, Željko Romić, Dario Rahelić
• Journal: Pharmacological research (Pharmacol Res) Vol. 65 Issue 4 Pg. 451-64 (Apr 2012) ISSN: 1096-1186 [Electronic] Netherlands
• PMID: 22214867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antioxidants
• Iridoid Glucosides
• Iridoids
• Pyrans
• oleuropein
• Carbon Tetrachloride
• Heme Oxygenase-1
• Superoxide Dismutase
• Glutathione

Topics

• Animals
• Antioxidants (therapeutic use)
• Carbon Tetrachloride
• Chemical and Drug Induced Liver Injury (drug therapy, metabolism, pathology)
• Disease Models, Animal
• Glutathione (metabolism)
• Heme Oxygenase-1 (metabolism)
• Iridoid Glucosides
• Iridoids
• Male
• Mice
• Mice, Inbred BALB C
• Oleaceae
• Oxidative Stress (drug effects)
• Pyrans (therapeutic use)
• Superoxide Dismutase (metabolism)