Date of Award

1966

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Pharmacy

First Advisor

John J. De Feo

Abstract

Toxicological investigations were conducted on two new antibiotics, Muconomycin A and Muconomycin B. These nonnitrogenous antibiotics were found to be highly toxic and capable of inducing profound inflammation in the peritoneal cavity of male albino rats. Either antibiotic produced large volumes \10-20 ml) of inflammatory exudate even when injected (i.p.) in quantities of 1.6 x 10-10 moles. An extensive profile of the electrolytes and proteins found in inflammatory exudates was developed./ Simultaneous assays of the blood serum of treated rats provided a basis for comparing the concentrations of constituents of serum with those of the exudate./ This approach to the study of the inflammatory response has not been previously described in such a comprehensive manner. /The results of these assays showed that the exudate contained lower concentrations of sodium and proteins, and greater amounts of potassium, calcium and phosphorus than the serum. Chloride ion concentrations were variable. It was hypothesized that the electrolyte and protein changes seen in these transudates would be reciprocally related to reported values for inflamed tissues. The data obtained in this research supported this hypothesis except in the case of chloride ion. The presence of large volumes of peritoneal fluid in these animals presented an opportunity to study water and electrolyte balances in a model state of ascites. This work confirmed the reported decrease in urine volume and electrolyte excretion seen in clinical ascites. A much greater retention of sodium than potassium was seen in this experimental ascites. The subcellular toxicity of these antibiotics was manifested as potent in vitro inhibition of the enzyme, ATP: creatine phosphotransferase.

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