Date of Award

1988

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Veterinary Physiology, Pharmacology, and Toxicology (Veterinary Medical Sciences)

First Advisor

Wayne Flory

Abstract

A comparative study of two susceptible species, the chicken and the rat, to crude and partially purified extracts of the plant Sesbania drummondii was undertaken. Partial physical and chemical characterization of crude sesbania extracts has been accomplished including temperature and pH stability, molecular weight fractionation and high pressure liquid chromatography and thin layer chromatography retention times. The toxicity of these different fractions could be differentiated with respect to weight loss, mortality, morbidity, serum protein changes and effect on PChE (Pseudocholinesterase) activities. The results indicated that more than one toxin exists in crude extracts of this plant. The pathophysiological findings could not be attributed to the presence of sesbanimide as the only major toxin of sesbania. The effects of sesbania extracts on serum protein concentration and PChE activity were similar but not identical to the effects of the protein synthesis inhibitor, cycloheximide. Additional qualitative and quantitative differences between the effects of sesbania extracts and cycloheximide were noted following histological and electron microscopic examination. The results suggested that inhibition of protein synthesis is not the only mechanism of sesbania intoxication. Some evidence was obtained to indicate that inhibition of export protein release from the liver occurred during sesbania intoxication. Further investigation suggested that the liver is a major target organ, though not the sole target organ, in an experimentally induced episode of sesbania intoxication. Phenobarbital gave partial protection against sesbania-induced weight loss and morbidity in the adult chicken but failed to protect the immature birds. No protective influence was noted for phenobarbital pretreatment in the sesbania treated rat. Evidence was obtained for the presence of several new microsomal glutathione-S-transferase isozymes which could be modified by sesbania treatment. Glutathione peroxidase activities were depressed by sesbania treatment. The induction of the cytochrome P-450 monooxygenase system by sesbania treatment in the chicken but not the rat suggested further species differences. The induction of the microsomal monooxygenase system and glutathione-S-transferases suggested the possibility of the release of free radicals or strong electrophiles by crude extracts of sesbania.

Pages

149

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