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Specific investigations: other studies

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Section 7.9.3 - Specific investiations: other: 
KS - mech.rat. Croutch & Christenson, 1999. KL.1;
SS - mech. in vitro. Freyberger, 1998. KS.2

Additional information

The mechanistic study (Croutch & Christenson, 1999) further characterises amicarbazone’s effects on the thyroid. In this study no treatment related effects were observed on the thyroid gland weight or microscopic changes observed in this organ at any treatment level. Thyroid to blood ratios of125I in treated groups were comparable throughout all treatment groups to the respective concurrent control groups, indicating the increase in thyroid hormones were most likely not due to increased synthesis, but rather differences in thyroid hormones being metabolised at another site. The liver is implicated as the extra-thyroidal site based on increased liver weights and UDP-glucuronosyltransferase activity. 

 

The results of the in vitro mechanistic study (Freyberger, 1998) support the conclusion that MKH 3586 does not affect the major enzymes involved in the synthesis or regulation of thyroid hormones, and strengthens the findings of thein vivosub-chronic mechanistic study which indicated that amicarbazone is conjugated by UDP- glucuronosyl transferase. This enzyme is also responsible for the conjugation of T3 / T4, therefore it would appear that amicarbazone competes for this enzyme with these thyroidal hormones. As a result less UDP- glucuronosyl transferase is available to conjugate T3 / T4, with serum levels increasing. This leads to hypertrophy of the liver, through the up regulation of UDP- glucuronosyl transferase.