Effects of the antioxidants dihydrolipoic acid (DHLA) and probucol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in vitro

Michael D. Coleman*, Claire D. Baker

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

The antioxidant effects of dihydrolipoic acid (DHLA) and probucol were investigated in a human erythrocytic in-vitro model of diabetic oxidative stress, where xenobiotics were used to form methaemoglobin. 4-Aminophenol mediated haemoglobin oxidation in non-diabetic erythrocytes was not affected by the presence of either DHLA or probucol. However, with diabetic cells, there were significant increases (P < 0.01) in 4-aminophenol-mediated haemoglobin oxidation in the presence of DHLA. Methaemoglobin formed by nitrite in non-diabetic and diabetic cells was not altered by either DHLA or probucol except at one time point in diabetic cells. In non-diabetic as well as diabetic cells, methaemoglobin formed by MADDS-NHOH was significantly reduced at all three time points in the presence of DHLA (P < 0.0001) but unaffected by probucol. In the presence of DHLA only, methaemoglobin formed by the products of rat microsomal oxidation of both 4-aminopropiophenone and benzocaine was markedly reduced for both xenobiotics in diabetic and non-diabetic cells (P < 0.0001) compared with cells incubated in the absence of DHLA. There were no significant differences between total cellular thiol levels determined between diabetic and non-diabetic erythrocytes, nor did DHLA or probucol affect resting thiol levels. MADDS-NHOH caused a significant thiol depletion in diabetic cells, which was restored in the presence of DHLA. A further study is required to determine how DHLA attenuates the potent REDOX reactions that occur during hydroxylamine-mediated methaemoglobin formation. © 2001 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)161-167
Number of pages7
JournalEnvironmental Toxicology and Pharmacology
Volume9
Issue number4
DOIs
Publication statusPublished - 17 Apr 2001

Keywords

  • antioxidants
  • diabetic and non-diabetic human erythrocytes
  • dihydrolipoic acid
  • methaemoglobin formation
  • probucol
  • xenobiotic

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