الفهرس 
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Abstract
Liver fibrosis is a common pathological process of hepatic disease, leading to the development of irreversible cirrhosis in humans and experimental animals. If treated properly at fibrosis stage, cirrhosis could be prevented. Liver fibrosis is characterized by increased deposition and altered composition of extracellular matrix, such that there is an excess of collagens. When advanced, the liver architecture is distorted by dense bands of collagens that link vascular structures and surround islands of regenerating parenchymal cells; these changes are characteristic of cirrhosis. Till now few effective, safe and convenient approaches for liver fibrosis are clinically available. In this study we offer a possible natural hepato-protective agent which can effectively ameliorate CCL4- induced liver fibrosis.
Several studies have demonstrated the anti-fibrogenic effect of interferon via inhibiting TGF-β expression, which decreases hepatic stellate cell activation and stimulates apoptosis . In the current study we demonstrate that the co-administration of JAT along with interferon and ribavirin can revert liver fibrosis more effectively.
In the present study, CCL4 treatment induced marked fibrosis and architectural distortion. CCl4 intoxication is the best known experimental model for liver injury so far. CCl4 administration can induce chronic liver damage in rats. It is metabolized by cytochrome P450 system to highly reactive trichloromethyl free radicals, which initiate liver cell destruction. Administration of CCl4 for 8 weeks resulted in a significant increase in serum ALT, AST activities as well as total billirubin levels. Theses
biomarkers showed major improvement to near normal values with triplet combination of interferon, ribavirin and Jerusalem artichoke, which is an indication of the stabilization of the plasma membrane and the repair of hepatic tissue damage caused by CCl4 intoxication. In the present study, Liver sections of animals intoxicated with CCl4 showed centrilobular congestion and ballooning degeneration, vacuolization and necrosis with loss of hepatocytes, leading to disintegration of hepatic cords with fibrosis as well as massive necrosis, accompanied with microvesicular steatosis and mononuclear cellular infiltration. Moreover, Masson’s trichrome stain of liver sections showed congestion and thickening of the portal tract with dense fibrous tissue.
Injury of hepatocytes results in the recruitment and stimulation of inflammatory cells, as well as resident ones, including Kupffer cells. Factors released by these inflammatory cells lead to activation of HSCs and their transformation into a myofibroblast-like phenotype. chronically activated HSCs produce large amounts of extracellular matrix proteins (ECM) and enhance fibrosis by secreting a broad spectrum of cytokines such as TGF-β1. This exerts pro-fibrotic actions in other cells and in an autocrine manner perpetuates their own activation. Our result also showed marked increase in the expression of TGF-β in CCL4 treated group.