Effect of kupffer cell modulation in rat liver fibrosis: histological and immunohistochemical study

ABSTRACT

The process of Ito cell activation, which is thought to be the central pathogenic mechanism in liver fibrogenesis, may involve distinct interactions with Kupffer cells [KCs] mediated by various cytokines and growth factors. The aim of the present study was to determine whether targeting KC function using gadolinium chloride [GdC13] interferes with the carbon tetrachloride [CC14]-induced hepatic fibrosis. Thirty-six male rats were divided into CC14 alone [group I]; CC14+GdC13 [group II]; and control groups, and were given CC14 only [0.3ml/kg, sc]; CC14+GdC13 [10mg/kg, ip]; or vehicles or GdC13 alone, respectively, for either 1 or 8 weeks. Hepatic injury was assessed by histological evaluation of the liver tissue, and by serum AST and ALT determination. Collagen and reticular fiber content of the liver was determined in Masson's trichrome-stained and silver-impregnated sections, respectively. In addition, activated Ito cells were detected by alpha-SMA immunohistochemistry. As expected, CC14 alone treatment resulted in a significant increase in connective tissue deposition in the liver [fibrosis], with a significant elevation of serum liver enzymes; massive cell necrosis; and an increase in alpha-SMA immunoreactive cells, especially after 8 weeks. In contrast, such manifestations of hepatic injury were significantly attenuated by simultaneous GdC13 administration, especially the fibrous tissue deposition. However, extensive fatty changes and cell death were still observed in one specimen. Therefore, it could be concluded that modulation of macrophage function may be a useful approach in the treatment of hepatic fibrosis