The mechanism by which vitamin A (VA, retinol) potentiates the hepatotoxicity of carbon tetrachloride (CCl₄) in male Srague-Dawley rats was investigated. The toxicity of single and repeated doses of CCl₄ was potentiated in rats following VA treatment. CCl₄-induced hepatotoxicity was completely eliminated in control and VA-treated rats by 1-aminobenzotriazole, a cytochrome P-450 inhibitor, indicating that CCl₄ metabolism was necessary to achieve potentiation. To determine if VA-potentiated CCl₄ hepatotoxicity involves retinol activation of Kupffer cells (KC), various parameters were measured as indicators of KC function. In vitro assays using populations of KC demonstrated that phagocytosis and free radical release were increased in KC isolated from VA-treated rats. A novel electrooptical technique for measuring release of superoxide anion (•O₂-) from individual KC was developed. It was demonstrated that KC are a heterogeneous population, each responding separately to a common stimulus. To examine if the mechanism by which VA potentiates CCl₄ hepatotoxicity is common to model systems in addition to Sprague-Dawley rats, four separate mice strains were also tested. VA pretreatment dramatically protected against CCl₄ toxicity in each mouse strain tested. These data support the hypothesis that in rats, release of reactive oxygen intermediates from KC is intimately involved in the mechanism by which VA potentiates CCl₄ hepatotoxicity.
| Identifer | oai:union.ndltd.org:arizona.edu/oai:arizona.openrepository.com:10150/186234 |
| Date | January 1993 |
| Creators | Mobley, Scott Alven. |
| Contributors | Sipes, I. Glenn, Earnest, David L., Gandolfi, A. Jay, Laird, Hugh E., II, Lantz, R. Clark |
| Publisher | The University of Arizona. |
| Source Sets | University of Arizona |
| Language | English |
| Detected Language | English |
| Type | text, Dissertation-Reproduction (electronic) |
| Rights | Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. |
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