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Comparative studies on the effect of noxythiolin and other thioureas on the thyroid using in vitro and in vivo models
1Celltox Centre, Hatfield Polytechnic, Herts, UK.
Abstract:
Noxythiolin (Noxyflex-S) inhibited iodide organification (thyroid hormone synthesis) by cultured porcine thyrocytes in vitro after 5 hr (IC50 approx. 9.0 microM). The positive control, the anti-thyroid thiourea methimazole, was about 15 times more potent an inhibitor of iodide organification (IC50 approx. 0.6 microM) under the same incubation conditions. In an in vivo assessment of follicular organification capacity using the perchlorate discharge test, 14 days of ip treatment of male Charles River rats with noxythiolin (50 mg/kg body weight) produced no inhibition of iodide organification when tested 24 hr after the last administration of noxythiolin whereas the positive control, propylthiouracil, was a highly potent inhibitor.
Insights
Noxythiolin demonstrated weak inhibition of thyroid hormone synthesis in vitro. In vivo studies showed no significant effect on iodide organification in rats, suggesting limited anti-thyroid activity.
Area of Science:
- Endocrinology
- Pharmacology
- Thyroid Research
Background:
- Thyroid hormone synthesis involves iodide organification, a critical step targeted by anti-thyroid drugs.
- Noxythiolin is a compound with potential therapeutic applications, necessitating an evaluation of its effects on thyroid function.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of noxythiolin on iodide organification, a key process in thyroid hormone synthesis.
- To compare the potency of noxythiolin with established anti-thyroid agents like methimazole and propylthiouracil.
Main Methods:
- In vitro assessment using cultured porcine thyrocytes to measure inhibition of iodide organification.
- In vivo evaluation in male Charles River rats employing the perchlorate discharge test to assess follicular organification capacity after 14 days of intraperitoneal noxythiolin administration.
Main Results:
- Noxythiolin exhibited moderate inhibition of iodide organification in vitro with an IC50 of approximately 9.0 microM.
- Methimazole, a positive control, was significantly more potent (IC50 approx. 0.6 microM) in inhibiting iodide organification in vitro.
- In vivo, noxythiolin treatment (50 mg/kg) did not inhibit iodide organification in rats 24 hours after the last dose, while propylthiouracil demonstrated potent inhibition.
Conclusions:
- Noxythiolin shows limited anti-thyroid activity in vitro and negligible effects on iodide organification in vivo.
- The findings suggest that noxythiolin is a weak inhibitor of thyroid hormone synthesis compared to established anti-thyroid drugs.
