Effects of lipoic acid and dihydrolipoic acid on 4-aminophenol-mediated erythrocytic toxicity in vitro.
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.
Coleman
Michael D
MD
School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK. m.d.coleman@aston.ac.uk
Williams
Charlotte
C
Haenen
Guido R M M
GR
D000328:Adult; D000627:Aminophenols / Q000633:toxicity*; D003979:Diazonium Compounds / Q000494:pharmacology; D004336:Drug Antagonism; D004912:Erythrocytes / Q000187:drug effects*; D006801:Humans; D008298:Maleates / Q000494:pharmacology; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013997:Time Factors
C504881:4-carboxyl-2,6-dinitrobenzenediazonium ion; D000627:Aminophenols; D003979:Diazonium Compounds; D008298:Maleates; D008063:Thioctic Acid; C015144:dihydrolipoic acid; C014476:diethyl maleate; C026729:4-aminophenol