الفهرس | Only 14 pages are availabe for public view |
Abstract This study was designed to investigate the potential effects of omega-3, olmesartan and their combination on established hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. Our results indicated that omega-3 and, to a lesser extent, olmesartan dose-dependently blunted CCl4-induced necroinflammation scoring and elevation of liver injury parameters in serum. Besides, omega-3 and, to a lesser extent, olmesartan treatments in a dose dependent manner attenuated CCl4-induced liver fibrosis, as demonstrated by hepatic histopathology scoring and 4-hydroxyproline content. The mechanisms behind these beneficial effects of both omega-3 and olmesartan were also elucidated. These include (1) counteracting hepatic oxidative stress and augmenting hepatic antioxidants; (2) preventing the activation of hepatic stellate cells (HSCs), as denoted by reducing a-smooth muscle actin (a-SMA) expression in the liver; (3) inhibiting the proliferation and chemotaxis of HSCs, as evidenced by downregulating platelet-derived growth factor receptors-b (PDGFR-b) expression in the liver; and (4) inhibiting the fibrogenesis response of HSCs, as indicated by inhibiting the secretion of transforming growth factor-b1 (TGF-b1). Unexpectedly, when olmesartan was co-administered with omega-3, it interfered with the hepatoprotective and anti-fibrotic activities of omega-3. In conclusion, this study introduces the first evidence regarding the pronounced anti-fibrotic activity of omega-3 and suggests that it may be beneficial in the treatment of hepatic fibrosis in humans. |