Effects of Lipoic Acid and Dihydrolipoic Acid on 4‐Aminophenol‐Mediated Erythrocytic Toxicity in vitro*

Abstract

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.

Dihydro-alpha-lipoic acid has more potent cytotoxicity than alpha-lipoic acid

“…Therefore, it is important to determine which is the active compound, ALA or DHLA, to exert various beneficial effects. It is known that ALA and DHLA do not show equivalent efficacy in several physiological activities (Muller and Menzel 1990;Lapenna et al 2003;Coleman et al 2006). The present study was performed to elucidate the differences in the cytotoxic activities of ALA and DHLA.…”

Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms

“…Dihydrolipoic acid inhibits tetrachlorohydroquinone‐induced tumor promotion via prevention of oxidative damage (Wang et al,2008). Conversely, other studies show that lipoic acid and DHLA induce apoptosis through promotion of intracellular oxidative stress (Wenzel et al2005; Coleman et al2006). In this study, we demonstrated that DHLA directly induces oxidative stress in ESC‐B5 cells (Fig.…”

Effects of Lipoic Acid and Dihydrolipoic Acid on Total Erythrocytic Thiols under Conditions of Restricted Glucose in vitro†

“…Although lipoic acid has been extensively investigated clinically and has been shown to be effective, it is capable of acting as a pro‐oxidant in certain conditions [8,26]. Although the closed system explored in this report is unlike the cellular environment in normal human erythrocytes, it is possible to speculate that in certain circumstances such as hypoglycaemia, high doses of lipoic acid might lead to depletion of cellular thiols, which could promote oxidative stress and cellular toxicity.…”