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

MD Coleman*, Claire A. Gaskin, Sandra Fernandes, Leena Khanderia

*Corresponding author for this work

Research output: Contribution to journalArticle

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. © 2002 Elsevier Science B.V. All rights reserved.

Original languageEnglish
Pages (from-to)15-19
Number of pages5
JournalEnvironmental Toxicology and Pharmacology
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 2003

Keywords

  • methaemoglobin
  • oxidant defence erythrocyte dapsone hydroxylamine
  • thyroxine
  • triiodothyronine

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