As previously described, the presence of the Fas ligand on the surface of the lymphocyte can activate Fas receptors normally expressed on the hepatocyte plasma membrane. There are several reports describing an increased expression of Fas in human specimens of chronic hepatitis C and B. Lymphocytes can also use the perforin-granzyme pathway to deliver their death signal. On the other hand, the role of viruses in the induction of apoptosis is controversial. Some authors have demonstrated that HCV proteins can induce apoptosis, whereas others have postulated that these proteins have the capacity to block the apoptotic signal generated by cytokines. Thus far, experimental models of HCV infection or replication have not shown evidence of increased hepatocyte cell death.
Hepatocyte apoptosis has also been demonstrated in human cholestatic disorders. Bile salts can induce hepatocyte apoptosis in vitro, and the same process has been identified in an animal model of extrahepatic cholestasis induced by bile duct ligation. Hepatocyte and bile duct apoptosis have been reported in primary biliary cirrhosis. Finally, there is experimental evidence that part of the protective effect of ursodeoxycholic acid in these disorders is explained by its capacity to block hepatocyte apoptosis.
There has been some degree of controversy concerning the importance of apoptosis in drug-induced liver injury. Earlier studies reported evidence of DNA fragmentation in hepato-cyte cultures exposed to toxic doses of acetaminophen, but most recent studies have concluded that oncotic necrosis is more important than apoptosis in this situation. You are always welcome to visit the best and most trusted pharmacy offering to canadian cialis online cialis professional 20 mg and giving you only most efficient medications with no rx required and fast delivery right to your doorstep.