Prevention of liver cirrhosis in rats by curcumin

Background and Aim: Curcumin, the major polyphenolic compound in turmeric, has been shown to attenuate hepatic damage in several animal models of liver injury. The aim of the present study was to examine the efficacy of curcumin in preventing thioacetamide-induced cirrhosis and to unravel the mechanism of curcumin’s effect on hepatic fibrosis in rats. Methods: Liver cirrhosis was induced by thioacetamide (TAA; 200mg/kg, i.p.) twice weekly for 12 weeks. One group of rats concomitantly received curcumin (300mg/kg/day, by gavage for 12 weeks); the control group received the solvent at identical amounts and duration. Results: TAA administration induced liver cirrhosis, which was inhibited by curcumin. Liver histopathology, hydroxyproline levels and spleen weights were significantly lower in the rats treated with TAA1curcumin compared with TAA only (Po0.001). Immunohistochemical studies and in situ hybridization demonstrated inhibition of hepatic stellate cell (a smooth muscle actin-positive) activation and collagen aI (I) gene expression in the livers of the TAA1curcumin-treated rats. Curcumin reduced oxidative stress as shown by the decreased hepatic nitrotyrosine staining in the curcumin1TAA-treated rats. Curcumin treatment had no effect on pre existing liver cirrhosis. As determined by in vitro studies using the rat HSC-T6 cell line, curcumin had no direct inhibitory effect on collagen a1 (I) messenger RNA expression. Further studies in these cells using reverse transcriptase-polymerase chain reaction demonstrated that curcumin had no effect on the expression of PDGF-induced TIMP-1 and TIMP-2, TGFb1, TGFb2 and MCP-1 but significantly inhibited tumor necrosis factor alpha expression. Curcumin had no effect on hepatic stellate cells proliferation. Zymography showed that curcumin had no effect on matrix metalloproteinase-2 activity. Conclusions: Curcumin inhibited the development of TAA-induced liver cirrhosis mainly due to its anti-inflammatory activities and not by a direct anti-fibrotic effect. As curcumin ingestion is safe in humans, it may be reasonable to assess in clinical studies the beneficial effect of curcumin in slowing the development of liver cirrhosis.