The use of xenobiotic-mediated methaemoglobin formation to assess the effects of thyroid hormones on diabetic and non-diabetic human erythrocytic oxidant defence mechanisms in vitro |
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Authors: | Coleman Michael D Gaskin Claire A Fernandes Sandra Khanderia Leena |
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Institution: | Mechanisms of Drug Toxicity Group, Department of Pharmaceutical Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK. |
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Abstract: | 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. |
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