Fas/FasL-dependent apoptosis of hepatocytes induced in rat and patients with Clonorchis sinensis infection.

To investigate the injury and pathogenesis of Clonorchis sinensis (C. sinensis) to hepatocytes, the liver samples from Wistar rats and patients with C. sinensis infection were examined. The typical histopathological findings of clonorchiasis were observed in rats 4 to 12 weeks postinfection, and majority hepatocytes exhibited hydropic degeneration, even some hepatocytes showed densely condensed nuclei suggesting apoptosis in liver tissue. Apoptosis was found around the central vein or portal areas of liver tissue in rat infected with C. sinensis by transferase uridyl nick end labeling (TUNEL) assay. Compared with normal control, TUNEL-positive cells in liver tissue increase from 4 to 12 weeks postinfection with the peak at 8 weeks. Furthermore, the expression of mRNA and protein of Fas, FasL, and caspase-3 was stronger in infected group than normal control using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Autopsy specimens from four patients infected with C. sinensis have the same findings detected by histopathology, TUNEL, and immunohistochemistry. These findings suggest that the C. sinensis can stimulate both hepatocytic apoptosis and hydropic degeneration that may be responsible for relationship between clinical manifestations and liver lesions in patients with clonorchiasis. These data also indicate a role for Fas/FasL-mediated pathway in the apoptosis that occurs in response to C. sinensis infection.