Effect of combined G6PD deficiency and diabetes on protein oxidation and lipid peroxidation

Naif S Karadsheh,Salem N Karadsheh,Nisreen A Quttaineh,Mohammad El-Khateeb

doi:10.1186/s12902-021-00911-6

Abstract

BackgroundOxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Since the incidence of G6PD deficiency in Jordan and many parts of the world is high, this study aimed to measure the effect of G6PD deficiency on the oxidative markers and the antioxidant glutathione (GSH) in diabetic and non-diabetic individuals.MethodsWhole blood G6PD deficiency was screened by the fluorescent spot method, and erythrocyte G6PD activity was determined using a quantitative assay. Since protein carbonyl (PC) and malondialdehyde (MDA) are the most widely measured markers for protein and lipid oxidation, respectively, plasma PC and MDA, in addition to blood GSH were determined by spectrophotometric assays, as biomarkers of oxidative stress.ResultsThe incidence of G6PD deficiency among the diabetic subjects was 15%. PC level in patients with diabetes and in G6PD-deficient subjects was 5.5 to 6-fold higher than in non-diabetic subjects with sufficient G6PD levels (p<0.001). This fold increase was doubled in diabetic patients with G6PD deficiency (p<0.001). Furthermore, the MDA level was significantly increased by 28-41% in G6PD-deficient, diabetics with sufficient G6PD, and diabetics with G6PD deficiency compared to MDA level in non-diabetic with sufficient G6PD. On the other hand, GSH was significantly reduced to half in G6PD-deficient subjects and in diabetics with G6PD-deficiency.ConclusionsThe results showed that diabetes and G6PD deficiency increased protein oxidation and lipid peroxidation. However, the combination of both disorders has an additive effect only on protein oxidation. On the other hand, GSH level is only reduced in G6PD deficiency. In addition, diabetes and G6PD deficiency appear to be genetically linked since the incidence of G6PD deficiency among people with diabetes is more than the general population.

Highlights

Oxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency
GSH level is not reduced in diabetic patients since it is likely to be maintained by the Nicotinamide adenine dinucleotide phosphate reduced (NADPH) supplied by the normal G6PD, hyperglycemia can promote Reactive oxygen species (ROS) accumulation through activation of multiple metabolic pathways: (1) increased flux of glucose through the polyol pathway, (2) increased formation of advanced glycation end products (AGEs), (3) activation of protein kinase C (PKC), and (4) increased hexosamine pathway flux [4]
The results showed that diabetes and G6PD deficiency increased protein oxidation and lipid peroxidation

Summary

Introduction

Oxidative Stress, an imbalance in the pro-oxidant/antioxidant homeostasis, occurs in many physiological and non-physiological processes and several human diseases, including diabetes mellitus (DM) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common hereditary disorder in humans, found mainly in people of Mediterranean, Southeast. G6PD deficiency is an X-linked disorder caused mainly by diverse point mutations. Few G6PD variants cause chronic hemolysis, the most common clinical manifestation of its deficiency is neonatal jaundice and oxidative stress-induced hemolytic anemia, caused by certain drugs and chemicals, infections, or ingestion of fava beans (Vicia faba) [1, 2]. More than 450 million people worldwide have diabetes mellitus (DM), the vast majority having type 2 DM. Hyperglycemia is one of the most important causes of oxidative stress and the production of oxidants. Increased oxidative stress has been suggested to contribute to the pathogenesis and development of diabetic complications [3, 4]

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