EFFECT OF DIFLUOROMETHYLORNITHINE ON THYROID FUNCTION IN RATS
Abstract
Background: A variety of stimuli cause a rapid increase in polyamine synthesis by increasing anenzyme ornithine decarboxylase required for the biosynthetic pathway of protein synthesis. Difluoromethyl ornithine is a selective inhibitor of this enzyme and hence arrests cell replicationstrikingly. Its effects on thyroid gland are studied with respect to change in animal’s weight andlevels of Triiodothyronine, Thyroxine and Thyroid stimulating hormone. The study was conductedto evaluate the inhibitory effects of Di-fluoromethyl ornithine (DFMO) administration onpolyamine metabolism of thyroid gland in rats. Methods: The study was conducted on ratsweighing 248 to 320 grams, divided into control and DFMO treated group. A dose of 50 mg/ratwas administered subcutaneously to the treated group for 5 consecutive days and placebo (normalsaline) injections to control group. On sixth day, blood was collected by cardiac puncture andserum was separated. Serum T3, T4 and TSH were analyzed with the help of radioimmunoassay inboth groups. Results: In treated group there was a fall in T3, T4 concentration with significant risein TSH concentration as compared to control group. Conclusion: DFMO (Difluoro methylornithine) decreases cellular proliferation of thyroid gland as is assessed by decrease in thyroidhormone levels. The hypothalamo pituitary thyroid axis however remains intact as is shown by afeedback rise in TSH concentration. DFMO can thus be employed for anti-neoplastic clinical trialson account of interference with activity of ODC (Ornithine Decarboxylase) fundamental forpolyamine biosynthesis.Keywords: DFMO, ODC, thyroid, rats, radioimmunoassayReferences
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