Changes in the concentration of tissue inhibitor of type 1 metalloproteinases in blood serum and liver of mice with CCl4-induced hepatitis

The concentration of tissue inhibitor of type 1 metalloproteinases in blood serum from intact CBA mice measured by enzyme immunoassay is similar to that in healthy humans. The concentration of tissue inhibitor of type 1 metalloproteinases in mouse bile was higher than in blood serum, while its concentration in liver homogenate more than 1000-fold exceeded that in the serum, which attests to its primarily intracellular localization in the liver. Loading of liver cell lysosomes with Triton WR-1339 and development of intrahepatic cholestasis did not affect the concentration of tissue inhibitor of type 1 metalloproteinases in liver homogenate and bile. Administration of CCl4 to mice for 4.5 weeks was accompanied by an increase in the concentration of tissue inhibitor of type 1 metalloproteinases in blood serum, but not in liver homogenate. These changes reflect dysregulation of metalloproteinases, development of inflammation, and progression of the initial stage of connective tissue formation in mouse liver.