Date of Award
Doctor of Philosophy
John T. Smith
Jane R. Savage, Mary Nelle Traylor, Michael H. Logan
This investigation was conducted to study the effect of acetaminophen on sulfur constituents in livers of rats fed various diets differing in respect to inorganic sulfate and methionine. Sodium 35SO4 = was administered to label ester sulfates, 35S-cysteine to label ester sulfates and neutral sulfur compounds other than methionine and 35S-methionine to label ester sulfates and neutral sulfur and by a precursor relationship give an indication of the effect acetaminophen may have on the remethylation pathway. Time of isotope injections were varied so that immediate synthesis of sulfur compounds could be evaluated as well as the effect the drug may have on tissue levels of sulfur compounds. Results from this investigation demonstrate that: (1) in acetaminophen-treated rats, liver sulfate is lowered to some constant level at which sulfate conjugation becomes rate limiting; (2) methionine is possibly drawn out of the remethylation pathway for synthesis of glutathione and cysteine; (3) inorganic sulfate may spare cysteine and possibly has the potential to inhibit the conversion of methionine to cysteine; and (4) inorganic sulfate fed at the 0.02% level with methionine supplementation is the optimal level which allows the liver to pull cysteine to glutathione for detoxication of acetaminophen. This investigation demonstrated the need for dietary inorganic sulfate as well as sulfur amino acids for acetaminophen detoxication, and that dietary levels of inorganic sulfate can inhibit of enhance the effect exerted by the drug depending on the level of inorganic sulfate and methionine.
Hodges, Julie Catherine, "Some Interrelationships Between Acetaminophen Detoxication and Dietary Sulfur Sources. " PhD diss., University of Tennessee, 1981.