| Popis: |
This series of studies examined the role of neutrophils and their proteases in Kepone/carbon tetrachloride (CD-CCl4) induced hepatotoxicity leading to mortality. The data demonstrate that neutrophils have an involvement in the hepatotoxicity induced by CD-CCl4, but are not causally linked to mortality. Neutropenia induced in female Sprague-Dawley rats maintained on a 10-ppm Kepone diet for 15 days prior to CCl4 (0.1 ml/kg, IP) reduced the hepatotoxicity by approximately 50%, but did not protect against lethality. A temporal examination of the infiltration of neutrophils demonstrated that neutrophils infiltrate in response to damage with the numbers of neutrophils infiltrating at the same rate regardless of the level of hepatotoxicity and/or mortality. The data also demonstrate that the CD-CCl4 interaction causes a reduction in acute phase proteins. In an attempt to substantiate the importance of the acute phase protein. depletion in the CD-CCl4 interaction, galactosamine (175 mg/kg, IP) was used to reduce the acute phase proteins. The galactosamine (175 mg/kg, IP) did not affect the hepatotoxicity of CCl 4 (0.3 ml/kg or 0.5 ml/kg, IP) in the order of magnitude as the CD diet. Turpentine, a general inducer of the acute phase response, administered 24 hours prior to the CCl4 is protective against both the hepatotoxicity and lethality associated with the CD-CCl4 nteraction. Although turpentine was protective, administering specific acute phase proteins did not demonstrate the same profound protection. [special characters omitted]-1-acid glycoprotein and [special characters omitted]-1-antitrypsin did not significantly reduce the hepatotoxicity and had no effect on the mortality. The combined data substantiates that neutrophils play a role in the interaction, but they are not solely responsible for the observed increases in hepatotoxicity or mortality. |
