Publication Year

1995

Keywords

Chemistry, endocrinology, rats, ovariectomy, osteopenia, x-ray

Disciplines

Chemistry | Endocrinology, Diabetes, and Metabolism | Medicine and Health Sciences

Abstract

This experiment was designed to evaluate the effects of continuous low level PGE2 infusion on osteopenia in the rat. The PGE2 was delivered via Alzet osmotic pumps at dosages of 1, 3, 6 mg/kg/day to ovariectomized rats. Three control groups were used which consisted of basal, aging, and ovariectomized rats. Throughout the course of the experiment, any abnormalities were noted in movement, eye grooming, hair quality, feces, leg edema, and facial edema. The changes in bone formation rates and density were determined with plain film x-ray evaluation and dual energy x-ray absorptiometry (DEXA). In order to verify that the pumps did function properly, the pumps were analyzed after the experiment to determine pump delivery. An additional in vitro experiment studied the effectiveness of the pumps as a delivery system as well. The PGE2 was determined to enter the circulatory system via a radio-immune assay (RIA) that tested for the presence of the PGE2 metabolite 13,14-dihydro-15-keto-prostaglandin E2. The pumps were found to function within the manufacturer's specifications although average experimental deliveries of PGE2 were found to be 0.66, 2.03, and 4.40 mg/kg/day. The presence of PGE2 induced severe symptomatic abnormalities single exception of front leg edema which was affected by the drug. Plain film x-ray evaluations found an increase in bone formation in both the femurs and tibias. DEXA analysis determined that there was a significant increase in bone mineral density (BMD) in the cortical areas of the femurs. Cancellous areas were found to show decreases in BMD which may be due to woven bone formation. Plain film x-ray evaluation published by Desimone et al. which stated that PGE2 controlled-release pellets implanted subcutaneously cause local inflammation, loss of cancellous bone in the tibia, no change in body weight, and no increase in PGE2 metabolite levels in the blood serum. The current experiment suggests that the pellets used by the Desimone group did not deliver PGE2 over the course of the experiment. Continuous low level PGE2 infusion via Alzet osmotic pumps caused increased overall bone formation in both the femur and tibia, increased PGE2 metabolite levels, severe symptomatic reaction, and decreased body weight. Prostaglandin E2 was determined to have a much greater anabolic effect when administered continuously than when injected intermittently.

Department 1 Awarding Honors Status

Chemistry

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