Wilson R, Buchanan L, Fraser W D, Jenkins C, Smith W E, Reglinski J, Thomson J A, McKillop J H
Department of Medicine, Glasgow Royal Infirmary, University of Strathclyde.
Autoimmunity. 1998;27(3):149-53. doi: 10.3109/08916939809003862.
There is evidence in the literature to support the view that antioxidants are involved in the pathogenesis of Graves disease and that antioxidants may act as free radical scavengers. This study has compared the effects of a 12 month course of conventional Carbimazole therapy on peripheral blood antioxidant levels with those of a 12 month course of a higher dose treatment regime. Fifty seven patients were enrolled into the study. Those in Group 1 (n = 23) received a 12 month course of 60 mg/day Carbimazole. Those in Group 2 (n = 34) received 45 mg/day for the first month, 30 mg/day for the second and 20 mg/day for the remaining 10 months of treatment. T3 was added in both groups after 2-4 months to maintain patients euthyroid. Baseline samples were also obtained from 30 control subjects. Blood samples were taken for the measurement of plasma thiol (PSH), lysate thiol (LSH), superoxide dismutase (SOD) and caeruloplasmin (CP) and for routine thyroid function tests (TT4, TT3 and TSH). In untreated Graves' patients, serum levels of PSH and SOD were reduced and levels of LSH increased compared to controls. Following 2 months high dose Carbimazole therapy there was a significant increase in PSH levels and a significant reduction in CP levels compared to presentation levels. In the more conventional dose Group 2 patients PSH levels also rose significantly during the first 2 months of treatment. Levels for both groups were still significantly lower than the control group. After 12 months high dose Carbimazole therapy PSH levels had decreased so that they no longer differed from untreated levels. LSH and SOD levels still remained abnormal. CP levels continued to fall. Similar findings were obtained in those patients receiving the more conventional course of treatment. At no point was their any significant difference in antioxidant levels between the two treatment groups. The abnormal levels of antioxidants in the serum of untreated Graves' patients confirm their involvement in the pathogenesis of Graves' disease. Carbimazole therapy appeared to have only short term effects on the peripheral blood levels of the antioxidants measured. Carbimazole appeared to act only on the extra cellular markers of antioxidant activity (PSH, CP) although the disease itself had marked intracellular effects (LSH, SOD). These findings suggest that Carbimazole does not act as a free radical scavenger.
抗氧化剂参与了格雷夫斯病的发病机制,且抗氧化剂可能起到自由基清除剂的作用。本研究比较了为期12个月的传统卡比马唑治疗方案对外周血抗氧化剂水平的影响与更高剂量治疗方案为期12个月的影响。57名患者参与了该研究。第1组(n = 23)患者接受为期12个月、每日60毫克卡比马唑的治疗。第2组(n = 34)患者在治疗的第1个月接受每日45毫克的剂量,第2个月接受每日30毫克,在剩余10个月的治疗中接受每日20毫克。两组在2 - 4个月后均添加T3以维持患者甲状腺功能正常。还从30名对照受试者中获取了基线样本。采集血样以测量血浆硫醇(PSH)、裂解物硫醇(LSH)、超氧化物歧化酶(SOD)和铜蓝蛋白(CP),并进行常规甲状腺功能测试(TT4、TT3和TSH)。与对照组相比,未经治疗的格雷夫斯病患者血清中的PSH和SOD水平降低,LSH水平升高。在高剂量卡比马唑治疗2个月后,与治疗前水平相比,PSH水平显著升高,CP水平显著降低。在采用更传统剂量的第2组患者中,治疗的前2个月PSH水平也显著升高。两组的水平仍显著低于对照组。高剂量卡比马唑治疗12个月后,PSH水平下降,以至于与未治疗时的水平没有差异。LSH和SOD水平仍异常。CP水平持续下降。接受更传统治疗方案的患者也有类似发现。两个治疗组之间的抗氧化剂水平在任何时候都没有显著差异。未经治疗的格雷夫斯病患者血清中抗氧化剂水平异常证实了它们参与了格雷夫斯病的发病机制。卡比马唑治疗似乎仅对所测量的外周血抗氧化剂水平有短期影响。卡比马唑似乎仅作用于抗氧化活性的细胞外标志物(PSH、CP),尽管疾病本身对细胞内有显著影响(LSH、SOD)。这些发现表明卡比马唑并非作为自由基清除剂起作用。