Morphology of liver stellate cells and liver vitamin A content in 3,4,3′,4′-tetrachlorobiphenyl-treated rats

Background/Aims: Because xenobiotics decrease the vitamin A stores localized in the liver stellate cells, we investigated morphological alterations in the liver of rats exposed to 3,4,3′,4′-tetrachlorobiphenyl. Special attention was given to the morphology of the liver stellate cells and to their relationship to the liver vitamin A content. Methods: Six rats received an intraperitoneal injection of 3,4,3′-4′-tetrachlorobiphenyl (300 μmol/kg) in soyabean oil. A further six rats received the vehicle alone. After 7 days, all rats were killed and their livers assayed for vitamin A. Liver stellate cells were examined and counted on liver sections, stained with toluidine blue or immunocytochemically for desmin and, for some animals, for α-smooth muscle actin. Results: In the livers of 3,4,3′,4′-tetrachlorobiphenyl-treated rats, we found spotty and bridging necrosis, with inflammation and accumulation of desmin-positive liver stellate cells. Steatosis and mild portal inflammation were also observed. 3,4,3′,4′-Tetrachlorobiphenyl decreased the liver vitamin A content by 38%, whereas morphometric analyses showed a 40% decrease of the number of toluidine blue-detected liver stellate cells and an 11% increase of desmin-detected liver stellate cells, indicating a likely differentation of liver stellate cells into myofibroblast-like cells. 3,4,3′,4′-Tetrachlorobiphenyl treatment did not modify the expression of α-smooth muscle actin. Morphological alterations were more pronounced in periportal than in pericentral areas. The liver vitamin A content was positively correlated (r=0.56, p<0.005) with the number of toluidine-blue detected liver stellate cells. Conclusions: 3,4,3′,4′-Tetrachlorobiphenyl administration results in an accumulation of liver stellate cells that start differentiating into myofibroblast-like cells. The 3,4,3′,4′-tetrachlorobiphenyl-induced decrease in liver vitamin A probably results from this differentiation, although other mechanisms cannot be excluded.