کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5851946 | 1561793 | 2013 | 9 صفحه PDF | دانلود رایگان |
The aim of this study was to investigate the therapeutic potential of rosmarinic acid (RA), a natural phenolic, in the treatment of acute liver toxicity. RA at 10, 25 and 50 mg/kg was administered by gavage once daily for 2 consecutive days, 6 h after CCl4 intoxication. CCl4 intoxication caused hepatic necrosis and increased serum ALT activity. In the livers, oxidative/nitrosative stress was evidenced by increased 3-nitrotyrosine (3-NT) and thiobarbituric acid reactive substances (TBARS) formation and a significant decrease in Cu/Zn superoxide dismutase (SOD) activity. CCl4 administration triggered inflammatory response in mice livers by activating nuclear factor-kappaB (NF-κB), which coincided with the induction of tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2). RA improved histological and serum markers of liver damage and significantly ameliorated oxidative/nitrosative stress and inflammatory response in liver tissue. Additionally, RA prevented transforming growth factor-beta1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) expression, suggesting suppression of profibrotic response. Furthermore, RA significantly inhibited the CCl4-induced apoptosis, which was evident from decreased cleavage of caspase-3. The hepatoprotective activity of RA coincided with enhanced NF-E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression. The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.
⺠CCl4-intoxication caused a severe liver damage in mice. ⺠Rosmarinic acid significantly ameliorated oxidative/nitrosative stress and apoptosis in the liver. ⺠Rosmarinic acid significantly suppressed inflammatory response in the liver. ⺠Rosmarinic acid prevented hepatic stellate cells activation and fibrogenesis.
Journal: Food and Chemical Toxicology - Volume 51, January 2013, Pages 370-378