Date of Award

1975

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology and Toxicology

Department

Pharmacology and Toxicology

First Advisor

Gary P. Carlson

Abstract

An asterosaponin extracted £rom. the Atlantic starfish Asterias forbesi (Desor) has been evaluated for pharmacological activity. The investigation has revealed that while the asterosaponin does not exhibit all the activities that would be expected, such as hemotoxicity to blood cells, cholinergic blocking activity, initiation of avoidance response reaction or production of autotomy, it does exhibit some unique properties not demonstrated by other asterosaponins. These activities include analgesia, anti-inflammation, and transient hypotension produced by a direct effect on the vascular bed. The bovine serum albumin assay for anti-inflammatory activity showed that a concentration of 500 μg/ml of asterosaponin caused an 85% inhibition 0£ protein denaturation. The rat paw edema assay demonstrated that pretreatment with asterosaponin at 75 mg/kg ip significantly reduced the edema caused by the carrageenin injection. In both cases the response was dose dependent. The analgesic activity of the asterosaponin was analyzed using the Koster acetic acid writhing test. Significant analgesia was demonstrated with a dose of asterosaponin as low as 15 mg/kg while 25 mg/kg was capable of reducing the writhes by 99%. The transient hypotensive activity of the asterosaponin was demonstrated in rats, cats, and dogs. Utilizing the cat it was demonstrated that very low doses of the asterosaponin (0. 5 mg/kg) could significantly transiently lower the blood pressure, but had no effect on the nictitating membrane or on somatic muscle contraction. The rat was less sensitive to the intravenously administered asterosaponin then the cat, eliciting a hypotensive effect only when concentrations of 4 . 0 mg/kg or higher were administered. The sensitivity of the dog to asterosaponin was intermediate. The dog exhibited a drop in blood pressure when a dose of 2. 0 mg/kg of asterosaponin was administered, and similar to the cat and rat showed a dose response relationship to the asterosaponin. The mechanism by which the asterosaponin caused the transient drop in blood pressure was investigated by an analysis of vagal influence, the possibility of histamine release, direct action on the vasculature and the possible complex involvement of some type of adrenergic blockade or stimulation using an experimental set up monitoring blood pressure, heart rate and ECG. The data showed that the asterosaponin continued to exhibit its hypotensive action even when the vagus nerves were severed, the animal was pretreated with antihistamine, the alpha receptors were blocked, or when the beta receptors were blocked. The hind leg perfusion experiment performed on the rat proved that the asterosaponin was acting directly on the vasculature. The experiment showed that the asterosaponin was capable of causing vasodilation directly when all neural influences were removed by cervical dislocation and severing, and was even capable of acting in the presence of beta blockade created by the administration of propranolol to levels which blocked isoproterenol effects.

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