کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2561585 1126940 2012 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Preventive and therapeutic effects of oleuropein against carbon tetrachloride-induced liver damage in mice
چکیده انگلیسی

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 (CCl4)-induced liver injury in male BALB/cN 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 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. CCl4 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.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacological Research - Volume 65, Issue 4, April 2012, Pages 451–464
نویسندگان
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