Determining a critical threshold for G6PD activity below which red blood cell response to oxidative stress is poor

Aim To study the oxidative modification of red blood cell Cu,Zn superoxide dismutase (SOD) in patients with ischemic heart disease (IHD) in vivo and in vitro to substantiate the use of a new oxidative stress marker.Material and methods Red blood cell Cu,Zn SOD was measured by depression of nitrotetrazolium blue reduction by the superoxide anion generated in xanthine oxidase xanthine oxidation. Red blood cell Cu,Zn SOD was measured immunochemically. The biochemical study was performed in the control group (patients with low extremity fracture without known history of cardiovascular diseases and hyperlipidemia) and in groups of patients with acute myocardial infarction, stable angina, and decompensated heart failure. For evaluation of oxidative stress intensity in IHD patients, an empirical SOD oxidative modification coefficient (OMCSOD) was proposed, which is a Cu,Zn SOD activity / Cu,Zn SOD content ratio.Results The red blood cell Cu,Zn SOD activity was significantly decreased in all IHD groups compared to the control group. Furthermore, OMCSOD was also considerably decreased in IHD patients, which warrants the use of this biochemical index as an oxidative stress marker.Conclusion It was shown that the Cu,Zn SOD modification was induced by interaction of the enzyme molecules with a natural dicarbonyl, malonic dialdehyde, and OMCSOD can be used for evaluation of oxidative stress intensity in IHD patients.

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Iron-deficiency anaemia enhances red blood cell oxidative stress

Free Radical Research ◽

10.1080/10715760802459879 ◽

2008 ◽

Vol 42 (9) ◽

pp. 824-829 ◽

Cited By ~ 80

Author(s):

Enika Nagababu ◽

Seema Gulyani ◽

Christopher J. Earley ◽

Roy G. Cutler ◽

Mark P. Mattson ◽

...

Keyword(s):

Oxidative Stress ◽

Iron Deficiency ◽

Blood Cell ◽

Red Blood Cell ◽

Iron Deficiency Anaemia ◽

Deficiency Anaemia

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Storage-induced increase in biomarkers of oxidative stress and inflammation in red blood cell components

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365513.2011.563789 ◽

2011 ◽

Vol 71 (4) ◽

pp. 299-303 ◽

Cited By ~ 20

Author(s):

Bülent Kücükakin ◽

Volkan Kocak ◽

Jens Lykkesfeldt ◽

Hans J. Nielsen ◽

Karin Magnussen ◽

...

Keyword(s):

Oxidative Stress ◽

Blood Cell ◽

Red Blood Cell ◽

Cell Components ◽

Biomarkers Of Oxidative Stress

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Polyphenolics enhance red blood cell resistance to oxidative stress: in vitro and in vivo1Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee by the US Department of Agriculture and does not imply its approval to the exclusion of other products that may be suitable.1

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/s0304-4165(00)00109-4 ◽

2000 ◽

Vol 1523 (1) ◽

pp. 117-122 ◽

Cited By ~ 119

Author(s):

K.A. Youdim ◽

B. Shukitt-Hale ◽

S. MacKinnon ◽

W. Kalt ◽

J.A. Joseph

Keyword(s):

Oxidative Stress ◽

Blood Cell ◽

Red Blood Cell ◽

Cell Resistance ◽

Department Of Agriculture ◽

Trade Name ◽

The Us ◽

Proprietary Product

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Determining a Critical Threshold for G6PD Activity below which RBC Response to Oxidative Stress is Poor

10.21203/rs.2.19598/v3 ◽

2020 ◽

Author(s):

Maria Swastika ◽

Alida R Harahap ◽

Lydia V Panggalo ◽

Sri Widia A Jusman ◽

Ari W Satyagraha

Keyword(s):

Oxidative Stress ◽

G6pd Deficiency ◽

Ex Vivo ◽

Strong Association ◽

G6pd Activity ◽

World Health ◽

Critical Threshold ◽

Main Function ◽

Oxidative Markers ◽

Significant Difference

Abstract Background Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder in the world. Its main function is to generate NADPH that is required for anti-oxidative pathway in the cells especially in red blood cells (RBC). G6PD deficiency is X-linked and thus subject to random X-chromosome inactivation in women giving them mosaic expression of G6PD activities in their individual cells. This phenomenon makes it difficult for diagnosis with the currently available G6PD qualitative diagnostic tests. With the rolling out of newly marketed anti-malarial drug tafenoquine, which has a long half-life, screening for G6PD deficiency becomes a necessity where those with <70% G6PD activity cannot receive this drug. Thus, evidence for a quantitative cut-off for G6PD activity is needed to ensure safe drug administration.Methods RBC models were developed to analyse the effect of oxidant on RBC oxidative markers namely total glutathione (GSH)and malondialdehyde (MDA). G6PD activity was measured using quantitative assay from Trinity Biotech and was correlated with cytofluorometric assay. RBC from twoG6PD heterozygous women with different G6PD activities were also analysed for comparison.Results There was a negative correlation between G6PD activity and CuCl concentration and a strong association between G6PD activities and proportion of G6PD normal RBC in CuCl-treated models and in ex vivo RBC. However, in terms of oxidative stress markers analyses, unlike the hypothesis where the lower G6PD activity, the higher MDA and the lower GSH level, the CuCl RBC model showed that in low G6PD activities (10-30%) cells, the MDA level is lower compared to the rest of the models (p<0.05). The ex vivo models however were in line with the hypothesis, although the result was not significant (p=0.5). There was a significant difference between RBC with <60% and those with >80% G6PD activities in CuCl RBC model, but not in ex vivo RBC (p=0.5). Genotyping heterozygous subjects showed G6PDViangchan variant with 2.97U/gHb (33% activity) and 6.58 U/gHb (74% activity). Conclusions The GSH analysis has pointed to the 60% G6PD activity cut-off and this data is supportive of the old World Health Organization threshold for intermediate upper limit of 60% G6PD activity. However, there are significant limitations in using MDA assay with CuCl RBC model because the RBC was already stressed due to the copper treatment and thus present a different result when compared to the ex-vivo model.

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