EFFECT OF DIFLUOROMETHYLORNITHINE ON THYROID FUNCTION IN RATS

Rehana Rehman, Rakhshaan Khan, Muhammad Saleh Soomro, Muhammad Aslam Aslam

Abstract


Background: A variety of stimuli cause a rapid increase in polyamine synthesis by increasing an
enzyme ornithine decarboxylase required for the biosynthetic pathway of protein synthesis. Difluoromethyl ornithine is a selective inhibitor of this enzyme and hence arrests cell replication
strikingly. Its effects on thyroid gland are studied with respect to change in animal’s weight and
levels of Triiodothyronine, Thyroxine and Thyroid stimulating hormone. The study was conducted
to evaluate the inhibitory effects of Di-fluoromethyl ornithine (DFMO) administration on
polyamine metabolism of thyroid gland in rats. Methods: The study was conducted on rats
weighing 248 to 320 grams, divided into control and DFMO treated group. A dose of 50 mg/rat
was administered subcutaneously to the treated group for 5 consecutive days and placebo (normal
saline) injections to control group. On sixth day, blood was collected by cardiac puncture and
serum was separated. Serum T3, T4 and TSH were analyzed with the help of radioimmunoassay in
both groups. Results: In treated group there was a fall in T3, T4 concentration with significant rise
in TSH concentration as compared to control group. Conclusion: DFMO (Difluoro methyl
ornithine) decreases cellular proliferation of thyroid gland as is assessed by decrease in thyroid
hormone levels. The hypothalamo pituitary thyroid axis however remains intact as is shown by a
feedback rise in TSH concentration. DFMO can thus be employed for anti-neoplastic clinical trials
on account of interference with activity of ODC (Ornithine Decarboxylase) fundamental for
polyamine biosynthesis.
Keywords: DFMO, ODC, thyroid, rats, radioimmunoassay

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