The antifibrotic effect of policosanol in CCl4-induced liver fibrosis in rats

Background: Liver fibrosis characterized with extreme accumulation of extracellular matrix proteins including collagen that occurs in most types of chronic liver diseases. Progressive liver fibrosis consequences in portal hypertension, liver failure and cirrhosis which often requires liver transplantation. Aim: This study was carried out to evaluate the antifibrotic effect of policosanol in liver fibrosis induced in rats by CCl4 administration. Material and methods: The rats were divided into four groups. Each group contains 10 Rats. The negative control group (NCG) received intra peritoneal (i.p.) injection of olive oil at dose of (0.1 ml/100 g BW) twice weekly for 8 weeks. The other three groups after induction of liver fibrosis by i.p. injection of 100% CCL4/ Olive Oil at dose of 0.1 ml/ 100g BW twice weekly for 8 weeks were divided into positive fibrotic group (PFG), policosanol treated group(PTG) and silymarin treated group(PTG). The positive fibrotic group remains without any treatment  Additionally, the policosanol and silymarin treated  groups were gavaged at dose of 100 mg/kg BW of either policosanol weekly twice dose for 8weeks according to previous report of  Silymarin dissolved in 0.5 percent CMC-Na as a daily dose for 8 weeks, Blood was drawn from the retro-orbital plexus through retro-orbital sinus puncture with a heparinized micro-hematocrit capillary tube, then centrifuged at 3000 rpm for 15 minutes to separate serum. Until biochemical analysis, they were kept at -20°C. Results : treatment of fibrotic rats with policosanol decrease level of ALT,AST  and Albumin as compared with Positive fibrotic group . we noticed that serum level of TGF-beta showed elevation in positive fibrotic group as compared by Negative control  group, while after treatment by policosanol or silymarin showed significant decrease, while serum levels of oxidative stress marker ( SOD) showed significant  reduction in positive fibrotic group as compared by Negative control  group but treatment with either policosanol or silymarin had significally increased those serum levels as compared by positive fibrotic group. Conclusion: Both silymarin and policosanol were found to have anti-fibrotic and antioxidant effects against CCL4-induced hepatic fibrosis, with the latter having a stronger effect than the former. Furthermore, we propose that, in addition to these pathways, the reduction of TGF-beta and Albumin, as well as an increase in liver enzymes and SOD, particularly in the PTG, might be considered as another key mechanism for developing therapeutic.