Reglinski J, Smith W E, Wilson R, Buchanan L M, McKillop J H, Thomson J A
Department of Pure and Applied Chemistry, Strathclyde University, Glasgow, UK.
Clin Endocrinol (Oxf). 1992 Oct;37(4):319-24. doi: 10.1111/j.1365-2265.1992.tb02331.x.
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.
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.
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.
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.
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.
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.
由于卡比马唑的确切作用机制尚不确定，因此利用核磁共振（NMR）光谱法研究了接受卡比马唑治疗疗程后的格雷夫斯病患者红细胞中的细胞变化。
使用从格雷夫斯病患者在卡比马唑治疗前、治疗后2个月和12个月获取的完整红细胞进行核磁共振光谱分析。数据与甲状腺激素和抗体水平相关联。
20例新诊断且先前未接受过治疗的格雷夫斯病患者（4例男性，16例女性）纳入研究。在治疗开始前以及治疗2个月和12个月后进行评估。在0个月和2个月时评估的20例患者中，只有12例完成了研究。
使用完整细胞的1H自旋回波核磁共振光谱法直接测量红细胞谷胱甘肽的氧化还原平衡。甲状腺激素和抗体水平采用报道的方法进行测量。
在2个月和12个月时，观察到红细胞谷胱甘肽有显著（P<0.01）氧化。在本研究评估的四个甲状腺相关标志物（T3、T4、TRAb和TSH）中，观察到T3（P<0.001）和TRAb（P<0.001）均与核磁共振观察到的谷胱甘肽变化相关。然而，体外实验表明卡比马唑不会直接影响红细胞谷胱甘肽。
提出了一个模型，该模型使用水合碘阳离子（I+），即T4转化为T3的天然产物，作为一种化学氧化剂，它可以在离体红细胞中产生观察到的细胞内谷胱甘肽的临床改变。提示卡比马唑在格雷夫斯病中的作用的一个主要因素可能是刺激脱碘酶的功能。
