Comparison of Erythrocyte Antioxidant Enzyme Activities and Embryologie Level of Neural Tube Defects

Abstract

Increased exposure to oxidant-derived free radicals or inadequate systems for antioxidant defense could alter cellular response at critical points in development. We measured 5 antioxidant enzymes, glutathione peroxidase (GSH-Px), glutathione reductase, glutathione-S-transferase, catalase and superoxide dismutase in erythrocytes and their plasma cofactor trace elements (Se, Zn, Cu) in 37 children with myelomeningocele and in 37 age-matched controls. We placed the patients into 3 groups according to motor level of the lesion at birth. We found significantly lower GSH-Px activities (p = 0.007) in children with myelomeningocele. For paired comparisons among the 3 patient groups and controls, there were significant differences (p < 0.05) between controls and both high (thoracic) and raid (lumbar) level embryologic lesions. The finding of antioxidant enzyme variations in our patients with myelomeningocele may indicate a role for abnormal oxidative metabolism in the development of this defect. The contribution of oxidative stress to human birth defects warrants investigation. We discuss potential relationships between oxidative stress and energy metabolism during primary neurulation.

Relationship of antioxidant enzyme activities with myelomeningocele

“…Only a few articles describing abnormal FRSE activities in infants with MM have been published (6,7,8,10). Previous studies measured FRSE activities, especially GSH-related reported a similar observation.…”

“…There was significantly lower GPX activity in children with MM (7). The studies of Graf et al (7,10,21) indicated that deficiencies of GPX are directly linked to neural tube defects. More recently, Graf and colleagues have demonstrated that GPX can be depressed in valporoic acid-treated patients (8).…”

“…Oxygen-derived FRs are important factors in the pathogenesis of many pediatric neurological diseases (6,7,10,24). Numerous studies have shown the relationship between FRs and neural tube defects (7, 8, 9, 10, 20, 29).…”

“…These enzymes play an active role in the detoxification of H 2 O 2 for the protection of cell against oxidative stress. The impaired responsiveness of the FRSE system plays a crucial role in oxygen-induced embryopathy and might result in MM (7,8,9,10,12,15,21). Erythrocyte FRSE are the most important enzymes in prevention of FRmediated neurological disease (6).…”

Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects

“…Many drugs that cause neural tube, and other, defects, including thalidomide [56], phenytoin [56,57], environmental aryl hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin [58], and ionizing radiation [59] induce oxidative stress. Myelomeningocele has been linked with reduced glutathione peroxidase activity apparently resulting from a genetic polymorphism [60]. Finally, maternal obesity, which could increase embryo oxidant exposure due to maternal glucose intolerance, has been found to increase the relative risk for NTD [61,62].…”