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Effects of Lipoic Acid and Dihydrolipoic Acid on 4‐Aminophenol‐Mediated Erythrocytic Toxicity in vitro *
Author(s) -
Coleman Michael D.,
Williams Charlotte,
Haenen Guido R. M. M.
Publication year - 2006
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.pto_499.x
Subject(s) - methemoglobin , thiol , lipoic acid , chemistry , toxicity , glutathione , oxidative stress , antioxidant , in vitro , biochemistry , enzyme , hemoglobin , organic chemistry
The effects of the antioxidant lipoic acid and its reduced form, dihydrolipoic acid (DHLA), were studied on the process of the erythrocytic toxicity of 4‐aminophenol in human erythrocytes in vitro . 4‐Aminophenol alone caused a stepwise increase in methaemoglobin formation, along with a commensurate decrease in total thiols. At 10 min., in the presence of lipoic acid alone and the thiol depletor 1‐chloro‐2,4‐dinitrobenzene (CDNB) alone, 4‐aminophenol‐mediated methaemoglobin formation was significantly increased, whilst thiol levels were significantly reduced compared with the 4‐aminophenol alone. At 10 min., with DHLA and CDNB alone, 4‐aminophenol was associated with significantly increased methaemoglobin formation. However, thiol levels were not significantly different in the presence of DHLA compared with 4‐aminophenol alone, although thiol levels were different compared with control (4‐aminophenol alone) in the incubations with CDNB alone. At 15 min., only CDNB/4‐aminophenol methaemoglobin formation differed from control, whilst thiol levels were significantly lower in the presence of CDNB alone compared with 4‐aminophenol alone. Lipoic acid enhanced the toxicity of 4‐aminophenol in terms of increased methaemoglobin formation coupled with increased thiol depletion, whilst DHLA showed increased 4‐aminophenol‐mediated methaemoglobin formation without thiol depletion. Lipoic acid, and to a lesser extent its reduced derivative DHLA, acted as a prooxidant in the presence of 4‐aminophenol, enhancing the oxidative stress effects of the amine in human erythrocytes.