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

Olives and olive products, an inevitable part of the Mediterranean diet, possess various beneficial effects. 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 (CCl4)-induced liver injury in mice. Oleuropein in doses of 100 and 200 mg/kg was administered intraperitoneally (ip) once daily for 3 consecutive days, prior to CCl4 administration (the preventive treatment), or once daily for 2 consecutive days 6 h after CCl4 intoxication (the curative treatment). CCl4 intoxication induced oxidative/nitrosative stress by down-regulating superoxide dismutase (Cu/Zn SOD) and inducible nitric oxide synthase (iNOS) activities and glutathione (GSH) levels. CCl4 administration triggered inflammatory response in mice livers by inducing expression of nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). In both treatment protocols, oleuropein attenuated oxidative/nitrosative stress and inflammatory response and improved histological and biochemical signs of acute liver damage. Additionally, in the curative treatment regimen, oleuropein prevented tumor necrosis factor-beta1 (TGF-β1) mediated activation of hepatic stellate cells (HSCs). The hepatoprotective activity of oleuropein was, at least in part, mediated through the induction of heme oxygenase-1 (HO-1). The present study demonstrate, for the first time, antioxidant, anti-inflammatory, and antifibrotic activity of oleuropein, with more pronounced therapeutic than prophylactic effects.

hepatotoxicity; oleuropein; oxidative stress; heme oxygenase-1; nuclear factor-kappaB; proinflammatory response

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