Date of Award


Degree Type


Degree Name

Master of Science in Pharmacology and Toxicology




Pharmacology and Toxicology

First Advisor

Gary P. Carlson


An extract from Eisenia bicyclis containing –principally a polyphenolic polymer was examined for pharmacological activity. The investigation centered around the established activity of a model polyphenolic compound, phloroglucinol. Studies on inflammation and alteration of hepatic microsomal enzyme activity were also performed. Heat denaturation of a 0.15% bovine serum albumin solution was inhibited 96% by the addition of the material at a final concentration of 0.32 mg/ml. Since stabilization of such solutions is often indicative 9f anti-inflammatory activity, direct measurements of this activity were made. The inhibition of formation of carrageenan-induced rat paw edema was utilized as a test system. As determined by paw volume changes, administration of a dose of 75 mg/kg (ip) one hour prior to carrageenan injection inhibited edema production by 88%. The potent anti-inflammatory agent phenylbutazone, at a dose of 90 mg/kg (ip), provided 100% protection. The protection given by the Eisenian extract apparently was not due to pituitary-adrenal stimulation, since the protection is 4-fold better than that given by a dose of 50 mg/kg ( ip ) of cortisone. The effect cannot be attributed to changes in body temperature, which remains unchanged. The effect can be partially but not completely attributed to the irritant properties of the material since buffering a dose of 100 mg/kg (ip) provided 42% protection. The effect is partially due to stabilization of the lysosomal membrane since in vitro 309 ug of the extract per milliliter of incubation media inhibited by 64% the release of the marker enzyme 8-glucuronidase from lysosomes. The compound administered at a dose of 75 mg/kg (ip) daily for 17 days offered no protection against rat paw edema induced by Freund's complete adjuvant. Capillary fragility was determined by mouse lung hemoglobin content following sudden decompression. No decrease in fragility was observed 1.5 hours after pretreatment with the extract at a dose of 300 mg/kg (ip). The material administered to mice (300 mg/kg, ip) 30 minutes prior to administration of lethal doses of curare exhibited p1"otection when the curare was also given by the intraperitoneal route . No protection was exhibited when the curare was administered subcutaneously. This suggested a chemical rather than a pharmacological antagonism. This hypothesis was supported when no antagonism was found to the action of curare on the cat gastrocnemius muscle in vivo by jugular infusion of 180 mg of the extract, and when a dose of 300 mg/kg (ip) one hour prior to sacrifice was found to have no effect on the activity of rat brain cholinesterase. The extract offered no antagonism to the action of either strychnine or tetrodotoxin. No change in rat liver microsomal enzyme activity, as determined by the extent of metabolism of 0-ethyl 0-(4-nitrophenyl) phenylphosphonothioate (EPN1 was found after the administration of 300 mg/kg (ip) of the material daily for 3 days. Also, a single injection of 300 mg/kg (ip) 1 hour prior to sacrifice for measurement of activity was without effect. Estrogenic activity was assayed by changes in uterine weight in the immature female rat. The administration of 300 mg/kg of the extract intraperitoneally daily for 3 days did not alter uterine weight. Rat liver homogenates were assayed for tryptophan pyrrolase activity by measuring the formation of the end product kynurenine. The administration of 300 mg/kg (ip) of the extract 1.5 hours prior to sacrifice caused 33% inhibition of the enzyme activity. The presence of the extract at a concentration of 486 μg/ml resulted in an in vitro inhibition of 82%.



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