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Date of Award

1981

Document Type

Thesis

Degree Name

Master of Science (M.S.)

Department

Graduate School

First Advisor

James Blankenship

Abstract

The polyamines are a group of natural compounds which have been found in almost all living tissues. N1- and N8- acetylspermidine have been known for a considerable time as normal constituents in human urine, but their physiological role is unknown. Recent studies have indicated the presence of enzymes in the tissues capable of converting spermidine into N1-acetylspermidine and N8-acetylspermidine and other enzyme activities which catalyze deacetylation and interconversion reactions.

One approach for determining physiologic activity of an endogenous compound is to observe their pharmacologic and toxicologic effects. In the present study, the LD50 for N1-acetylspermidine, N8-acetylspermidine, spermidine, spermine and putrescine, were determined by intraperitoneal injection in mice. The LD50 for N1-acetylspermidine •2HCl and N8-acetylspermidine •2HCl were 1150 and 820 mg/kg, respectively, and the respective LD50 for spermidine •3HCl, spermine n#8226;4HCl and putrescine n#8226;2HCl were 870, 370, and 1400 mg/kg.

The major difference between the toxicity of N1-acetylspermidine and N8acetylspermidine and that of spermidine, spermine and putrescine appeared to be the latency period for the time of death. While N1- and N8-acetylspermidine have very rapid effects in which animals died in the first ten minutes after the injection with very few delayed deaths, the effects of spermidine, spermine and putrescine occurred over a wider range of time intervals with some deaths occurring as late as ten days after treatment

The other signs of toxicity with N1acetylspermidine, N8-acetylspermidine, spermidine, spermine, and putrescine were qualitatively quite similar as each compound produced hypothermia, sedation, muscle incoordination, decreased motor activity, decreased respiration, and clonic convulsions.

Pages

111

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