Spin echo nuclear magnetic resonance studies on intact erythrocytes: changes in cellular metabolism as a consequence of carbimazole therapy.
OBJECTIVE
Because the exact mechanism of action of carbimazole is uncertain, nuclear magnetic resonance (NMR) spectroscopy was used to investigate cellular changes in erythrocytes from Graves' patients following a course of carbimazole therapy.


METHODS
NMR spectroscopy was carried out using intact erythrocytes obtained from Graves' patients prior to and at 2 and 12 months after carbimazole treatment. The data were correlated with thyroid hormone and antibody levels.


METHODS
Twenty patients (four males; 16 females) with newly diagnosed and previously untreated Graves' disease were enrolled into the study. Assessments were made prior to the commencement of therapy and after 2 and 12 months on treatment. Of the 20 patients assessed at 0 and 2 months only 12 completed the study.


METHODS
The oxidation-reduction balance of erythrocyte glutathione was measured directly using 1H spin echo NMR spectroscopy of intact cells. Thyroid hormone and antibody levels were measured using reported methods.


RESULTS
At 2 and 12 months a significant (P < 0.01) oxidation of the erythrocyte glutathione was observed. Of the four thyroid related markers (T3, T4, TRAb and TSH) assessed in this study both T3 (P < 0.001) and TRAb (P < 0.001) were observed to correlate with the NMR observed changes in glutathione. However, in-vitro experiments indicated that carbimazole does not affect red cell glutathione directly.


CONCLUSIONS
A model is presented which uses the hydrated iodium cation (I+), the natural product of T4 conversion to T3, as a chemical oxidant which can produce the observed clinical alteration in intracellular glutathione in ex-vivo erythrocytes. It is suggested that a major factor in the action of carbimazole in Graves' disease may be to stimulate the function of the deiodinase enzymes.
Reglinski
J
J
Department of Pure and Applied Chemistry, Strathclyde University, Glasgow, UK.
Smith
W E
WE
Wilson
R
R
Buchanan
L M
LM
McKillop
J H
JH
Thomson
J A
JA
D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D002231:Carbimazole / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006111:Graves Disease / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D013972:Thyrotropin / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism
D001323:Autoantibodies; D018828:Immunoglobulins, Thyroid-Stimulating; D014284:Triiodothyronine; D002231:Carbimazole; D013972:Thyrotropin; D005978:Glutathione; D013974:Thyroxine