Date of Award

1973

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

Gary P. Carlson

Abstract

A series of vinyl sulfone molluscicidal agents was tested to determine the ability to interfere with: a) the color-forming reaction between cysteine and 5,5’–dithiobis (2-nitrobenzoic acid) (DTNB); b) the activity of malic dehydrogenase, a typical sulfhydryl-dependent enzyme; c) the in vitro endogenous respiration in the snail, Australorbis glabratus; and d) the in vivo and in vitro endogenous respiration and pyruvate metabolism of liver, brain, and kidney of albino rats. An approximate intraperitonea LD50 was determined for vinyl sulfone in male and female albino rats. The effect of vinyl sulfone on cysteine treated albino rats was also observed. Vinyl sulfone and derivatives were found to inhibit the color-forming reaction between cysteine and DTNB indicating sulfhydryl reactivity. A positive correlation between this in vitro sulfhydryl reactivity and molluscicidal potency was observed. However, no significant effect on endogenous respiration was observed in A. glabratus . Similarly, no significant effects on endogenous respiration or pyruvate metabolism were observed in the tissues tested from male and female albino rats. High concentrations of vinyl sulfone were required to significantly inhibit the activity of malic dehydrogenase. An intraperitoneal LD50 of 3 mg/kg vinyl sulfone was found for male and female albino rats. A sublethal dose of vinyl sulfone was found to cause increased blood urea nitrogen and decreased urinary output in albino rats while producing no significant effects on SGOT, SGPT, and hematocrit levels. These data indicate that the toxicity of vinyl sulfone and derivatives is related to sulfhydryl reactivity; however, this toxicity was not due to decreased endogenous respiration in either A. glabratus or albino rats. The toxicity of sublethal doses of vinyl sulfone was postulated to be caused by the impairment of normal renal function. A hypothesis was proposed that the toxicity of vinyl sulfone and derivatives in A. glabratus may be due to the reaction of these agents with integral membrane proteins responsible for normal cellular function.

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