Mechanisms of Drug Toxicity Group, Department of Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Environ Toxicol Pharmacol. 2003 Jan;13(1):15-9. doi: 10.1016/s1382-6689(02)00108-4.
Diabetes is associated with an abnormal incidence of hypothyroidism, which exacerbates hyperglycaemia, so further damaging already compromised erythrocytic defence mechanisms. Methaemoglobin formation is a useful measure of the health of these mechanisms, as it determines the resistance of diabetic erythrocytes to sustained oxidative stress. The effect of l-tri-iodothyronine (T(3)) was, therefore, studied on nitrite and monoacetyldapsone hydroxylamine (MADDS-NHOH) mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes. Diabetic erythrocytes showed less sensitivity compared with non-diabetics to methaemoglobin formation mediated by both compounds. A 30 min pre-incubation with T(3) at 3 and 30 nM did not affect nitrite-mediated methaemoglobin formation compared with control observations in both cell types. In diabetic erythrocytes incubated with T(3) at 30 nM, there were significant increases in MADDS-NHOH-mediated methaemoglobin formation compared with control in both diabetic and non-diabetic cells. Studies comparing blood isolated from diabetic patients stabilised on thyroxine (T(4); 50 μG/day), T(4)-free diabetics and non-diabetics, showed that T(4) supplementation significantly increased MADDS-NHOH-mediated methaemoglobin formation compared with T(4)-free diabetic cells so that for two time points, T(4)-treated diabetic erythrocytic methaemoglobin formation was indistinguishable from that of non-diabetics. These studies indicate that T(4) supplementation improves some erythrocytic oxidant defence mechanisms in a time dependent manner.
糖尿病与甲状腺功能减退症的异常发病率有关，后者会加重高血糖，从而进一步损害已经受损的红细胞防御机制。正铁血红蛋白的形成是衡量这些机制健康状况的有用指标，因为它决定了糖尿病患者红细胞对持续氧化应激的抵抗力。因此，研究了 l-三碘甲状腺原氨酸 (T(3)) 对糖尿病和非糖尿病人类红细胞中亚硝酸盐和单乙酰二苯砜羟胺 (MADDS-NHOH) 介导的正铁血红蛋白形成的影响。与非糖尿病患者相比，糖尿病患者的红细胞对这两种化合物介导的正铁血红蛋白形成的敏感性较低。在 3 和 30 nM 下用 T(3)预孵育 30 分钟与两种细胞类型的对照观察相比，不会影响亚硝酸盐介导的正铁血红蛋白形成。在 30 nM T(3)孵育的糖尿病红细胞中，与糖尿病和非糖尿病细胞的对照相比，MADDS-NHOH 介导的正铁血红蛋白形成显著增加。比较在甲状腺素 (T(4); 50 μg/天) 稳定的糖尿病患者、无 T(4)的糖尿病患者和非糖尿病患者分离的血液的研究表明，T(4)补充剂显著增加了 MADDS-NHOH 介导的正铁血红蛋白形成与无 T(4)的糖尿病细胞相比，以至于在两个时间点，T(4)治疗的糖尿病红细胞正铁血红蛋白形成与非糖尿病患者无法区分。这些研究表明，T(4)补充剂以时间依赖的方式改善了一些红细胞抗氧化防御机制。
