Date of Award

1999

Degree Name

Chemistry

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Leslie Frost

Second Advisor

Ernest M. Walker

Third Advisor

Michael Norton

Abstract

Benign chemical agents for removing iron from people with iron-overload diseases are lacking; thus the purpose of this investigation is to evaluate the toxicity of acetaminophen in iron-overloaded mice compared to normal mice and to evaluate the iron-mobilizing ability of this agent in an iron-overloaded mouse model. Female Hilltop (ICR) CVF mice, ranging between six months to one year of age, were used in these experiments. Mice were given intraperionteal(ip) injections of 300 mg/kg ferric hydroxide-dextran complex for a total of five, eight, or thirteen injections to achieve an iron-overloaded state. Iron-overloaded mice were given ip injections of either 350,200, 175, 150, or 100 mg/kg acetaminophen for a total of up to twenty injections. Also, a group of non-iron-overloaded mice received these injections of acetaminophen at the same time. Negative controls (no iron, no acetaminophen) and positive controls (iron only) groups were included. Livers were obtained at autopsy from mice in all groups with samples submitted for iron staining and other samples for elemental analysis using ICP-AES techniques. Blood was obtained to measure hematocrits and liver function tests.

Results of these studies suggest that excess liver iron stores may in some way reduce acetaminophen-induced hepatic toxicity. Also, the removal of hepatic iron was noted in some cases and a mechanism for this removal has been proposed. In vitro studies of the interaction of acetaminophen and iron(III) were performed using ultraviolet-visible absorption spectroscopy. Evidence of the production of a transient species, resulting from this interaction is reported here.

Subject(s)

Iron -- Effect of acetominophen on.

Chemistry, Inorganic.

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