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The effect of an acute phase response on the toxicity of mechanistically distinct toxins
Two scenarios for stimulating the acute phase response (APR), subcutaneous (s.c.) injection of turpentine and s.c. injection of carrageenan, were tested for their ability to protect against a range of toxic conditions that reflect distinct mechanisms. Five hepatotoxins were included: the chlordecone/carbon tetrachloride interaction (CD/CCl4), CCl4 alone, galactosamine (GalN), allyl alcohol (AA) and thioacetamide (TA). The nephrotoxin, mercuric chloride (HgCl2) was also included. Each group of Sprague-Dawley rats was administered one of six toxins following a 24-hour prior treatment with either turpentine, carrageenan, or with no prior treatment (toxin alone). Toxicity was evaluated by serum alanine transaminase (ALT) and histology (hematoxylin-eosin) at 12-hour intervals over 48 or 72 hours. The APR was monitored by serum haptoglobin (Hp) and ceruloplasmin (Cp) at 12-hour intervals over the same periods. The temporal relationship between APR-induction and toxicant administration was modified in two additional experiments: (1) simultaneous injection of turpentine and toxicant and (2) turpentine injected 12 hours after administration of the toxin. Results indicate that turpentine or carrageenan injected 24 hours prior to toxicant profoundly reduced the hepatotoxicity (89 to 99%) of CCl4, CD/CCl4, GalN and TA when compared to toxin alone. Protection corresponds to significant, often multifold, increases in Cp and Hp. Both turpentine and carrageenan failed to protect against AA and HgCl2 toxicity, despite elevated APPs. Finally, turpentine failed to protect against toxic exposure when the temporal relationship between turpentine injection and toxicant administration was modified as in cases 1 and 2, where Cp and Hp responses had not fully developed.
Ewald, Kathryn A, "The effect of an acute phase response on the toxicity of mechanistically distinct toxins" (2000). Doctoral Dissertations Available from Proquest. AAI9960749.