Effects of oxidised α-lipoic acid and α-tocopherol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in-vitro

Coleman, Michael D.; Walker, Charlotte L

doi:10.1016/s1382-6689(00)00034-x

Cited by 11 publications

(4 citation statements)

References 26 publications

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“…That DHLA and lipoic acid actually prevent haemoglobin oxidation occurring, rather than reducing methaemoglobin itself could be supported by the inability of DHLA or lipoic acid to directly reduce methaemoglobin to haemoglobin in vitro. 17,18 However, if DHLA had diverted more hydroxylamine to amine, this should have increased amine detection in the erythrocytes, which did not occur in this study. Alternatively, it is conceivable that again, neither agent prevents methaemoglobin formation, but they activate erythrocytic reductive enzyme systems, such as NADH and NADPH dependent methaemoglobin reductases.…”

Section: Time (Minutes)mentioning

confidence: 59%

“…5,13 Due to their compromised antioxidant systems, diabetic erythrocytes form less xenobiotic-mediated methaemoglobin than non-diabetic cells, so any potentially beneficial effects of exogenous antioxidants can be studied in terms of changes in methaemoglobin formation and changes in thiol status. [14][15][16] Previous studies have evaluated lipoic acid 17 as well as dihydrolipoic acid (DHLA) 18 for their effects on methaemoglobin in this experimental model. The present study has evaluated the effects of these agents and ascorbate on xenobiotic-mediated methaemoglobin formation and resting erythrocytic glutathione (GSH) levels in human diabetic and non-diabetic erythrocytes in vitro.…”

Section: Introductionmentioning

confidence: 99%

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Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

Coleman

Tolley

Desai

2001

Diabetes & Vascular Disease

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Deficiencies in the reducing power of diabetic erythrocytes can be studied using the sulphone metabolite, monoacetyl dapsone hydroxylamine (MADDS-NHOH) to generate methaemoglobin, which is a form of oxidative stress. The effects of three antioxidants, dyhydrolipoic acid (DHLA), lipoic acid and ascorbate were compared using this method in erythrocytes of type 1 diabetic patients. During 2-hour incubations, DHLA and lipoic acid significantly reduced MADDS-NHOH-mediated methaemoglobin formation to the same extent in diabetic and non-diabetic erythrocytes. In contrast, ascorbate markedly increased MADDS-NHOH-mediated methaemoglobin formation at all time points up to 2 hours for diabetic cells and 15—60 minutes in non-diabetic erythrocytes. Ascorbate abolished the deficiency in methaemoglobin sensitivity normally seen in diabetic erythrocytes compared with non-diabetic erythrocytes. During a 1-hour pre-incubation period, neither DHLA, lipoic acid nor ascorbate significantly altered total thiol concentrations. After a 2-hour incubation with MADDS-NHOH, thiol concentrations did not significantly change in the non-diabetic erythrocytes, but they fell significantly in the diabetic cells. Diabetic and non-diabetic erythrocytes pre-incubated with ascorbate, DHLA and lipoic acid showed no changes in thiol levels in the presence of MADDS-NHOH. In summary, ascorbate, DHLA and lipoic acid showed contrasting effects on methaemoglobin generation, although they each abolished the diabetic erythrocytic deficit in total thiol status caused by hydroxylamine-mediated methaemoglobin formation. This work provides evidence for the potential future use of antioxidant supplements in diabetic management.

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Section: Time (Minutes)mentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

Coleman

Tolley

Desai

2001

Diabetes & Vascular Disease

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“…Indeed, previous studies with lipoic acid and other methaemoglobin formers suggest that lipoic acid‐mediated prooxidant effects during methaemoglobin formation may be dependent on two major factors: firstly, the type of methaemoglobin former employed and secondly, on the contact time with the erythrocytes. Although nitrite‐mediated methaemoglobin formation follows different kinetics and reaction processes compared with the effects of many aromatic amines, (Coleman 2000), lipoic acid accelerated nitrite‐mediated methaemoglobin formation, whilst its reduced derivative DHLA did not (Coleman & Walker 2000; Coleman & Baker 2001). The effects of lipoic acid in the erythrocyte appear to be time‐dependent.…”

Section: Discussionmentioning

confidence: 99%

“…With identical reagent concentrations and a 60 min. pre‐incubation, the antioxidant actually caused a reduction in 4‐aminophenol‐mediated methaemoglobin formation (Coleman & Walker 2000). Cellular metabolism of lipoic acid is complex, as it binds to many cellular proteins and is converted to DHLA by the glutathione system (Packer et al 1995; Hermann et al 1996).…”

Section: Discussionmentioning

confidence: 99%

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

Coleman

Williams

Haenen

2006

Basic Clin Pharma Tox

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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.

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Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

Al-Rasheed

Attia

et al. 2013

J Physiol Biochem

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Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg(-1) day(-1)) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P < 0.01) together with a significant elevation (P < 0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA + STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.

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Effects of oxidised α-lipoic acid and α-tocopherol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in-vitro

Cited by 11 publications

References 26 publications

Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

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

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

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Effects of oxidised α-lipoic acid and α-tocopherol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in-vitro

Cited by 11 publications

References 26 publications

Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †

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

Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?

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