Immune system-mediated endothelial damage is associated with NO and antioxidant system disorders

Abstract

Two distinct systems of different origin are involved in the pathogenesis of both infectious and immunological vasculitis syndrome: nitric oxide (NO) from endothelial cells and granulocyte NADPH oxidase. In this study, in 31 children with immune system dysfunction, NO, NO synthase (NOS) and antioxidant enzyme activities [catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx)], as well as immunological parameters, were investigated. On the basis of the clinical findings, all children were divided into three groups: group I, 8 children clinically showing macular skin manifestations; group II, 11 children with maculo-papulous changes; and group III, 12 children with clinical findings of papulous changes. Plasma NO values in groups II and III were significantly elevated (79.14+/-30.13 and 65.32+/-6.70 micromol/l), compared to the control group (41.24+/-3.65 micromol/l), while group I showed statistically lower values (32.38+/-3.37 micromol/l). In children with the highest level of NO (group II) NOS activity was two-fold higher (1.77+/-0.59 nmol/ml/min; p<0.01) than in controls (0.98+/-0.23 nmol/ml/min). Catalase activity showed a significant increase and SOD activity a significant decrease in all experimental groups, while GPx was not significantly changed. The results show that immune system dysfunction manifested as vasculitis is associated with significant disturbances in the NO system and free radicals scavengers.

Markers of oxidative and nitrosative stress in systemic lupus erythematosus: Correlation with disease activity

“…Increased formation of nitrated protein thus presents another important potential mechanism in the pathogenesis of SLE. Furthermore, excessive ·NO production as a result of activation of iNOS is assumed to contribute to SLE and other autoimmune diseases, mainly via reaction with superoxide to form ONOO − (22, 23, 32, 48, 49). There is growing evidence that the overexpression of iNOS is associated with the development and progression of autoimmune diseases in experimental animal models (22, 23, 27).…”

Biomarkers for Oxidative Stress: Clinical Application in Pediatric Medicine

“…Allergic/Immunologic: atopic dermatitis [21*, 58*], bronchial asthma [40,51,74], chronic arthritis [15,85], Henoch-Schonlein purpura [37], Kawasaki disease [48], systemic lupus erythematosus [68], vasculitis syndrome [73] Oxidative tissue injury from pathological conditions might have more serious consequences in young people (especially children) than in older people because of the need for subsequent tissue growth to match somatic growth and because survival is longer in young people than in older people. Primary and secondary prevention of oxidative damage might therefore be important, especially in young people.…”

“…Malfunction of the NO system is implicated in numerous disease processes, resulting in reduced [21, 55,64] or excessive NO production [20,34,39,43,44,73,85,88,94,114]. The NOS substrates, i.e., L-arginine and BH 4 , can be administered to enhance NO production; increased NO levels can be achieved directly through administration of NO donors.…”

Oxidative Stress and Overview of Pediatric Disease Biomarkers

“…Under normal physiologic states, the balance between ROS generation and ROS elimination is maintained by antioxidant enzymes and nonenzymatic antioxidants. 10 Antioxidants in biological systems can be classified into three groups: enzymes, proteins, and low-molecular-weight proteins. Antioxidant enzymes are SOD, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase (GST), thioredoxin reductase, and hemeoxygenase.…”