Evidence for carbimazole as an antioxidant?
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.
Wilson
R
R
Department of Medicine, Glasgow Royal Infirmary, University of Strathclyde.
Buchanan
L
L
Fraser
W D
WD
Jenkins
C
C
Smith
W E
WE
Reglinski
J
J
Thomson
J A
JA
McKillop
J H
JH
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D013956:Antithyroid Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002231:Carbimazole / Q000008:administration & dosage / Q000627:therapeutic use*; D016022:Case-Control Studies; D002570:Ceruloplasmin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D013438:Sulfhydryl Compounds / Q000097:blood; D013482:Superoxide Dismutase / Q000097:blood
D000975:Antioxidants; D013956:Antithyroid Agents; D016166:Free Radical Scavengers; D013438:Sulfhydryl Compounds; D002231:Carbimazole; D013482:Superoxide Dismutase; D002570:Ceruloplasmin