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Apoptosis and antioxidant defense in the nephrotic syndrome
Jacek Zachwieja1, Waldemar Bobkowski, Marcin Zaniew
1Department of Nephrology, Institute of Pediatrics, Karol Marcinkowski University of Medical Sciences, Szpitalna 27/33 Strasse, 60-572 Poznan, Poland. zachwiej@mp.pl
Insights
Children with nephrotic syndrome (NS) show reduced antioxidant defenses, leading to increased T lymphocyte apoptosis. This study highlights the link between oxidative stress and immune cell dysfunction in NS patients.
Area of Science:
- Immunology
- Pediatrics
- Biochemistry
Background:
- Nephrotic syndrome (NS) is associated with T lymphocyte dysfunction.
- Oxidative stress may play a role in the pathogenesis of NS.
Purpose of the Study:
- To investigate antioxidant status in children with NS.
- To determine the influence of antioxidant status on T cell apoptosis in NS.
Main Methods:
- Studied 57 children with NS (first episode and remission) and 26 controls.
- Assessed T lymphocyte apoptosis using Annexin V-FITC.
- Measured plasma total antioxidant status (TAS) and red blood cell glutathione reductase (GR) and glutathione peroxidase (GPX) activity.
Main Results:
- Children with a first episode of NS had significantly reduced TAS, GR, and GPX activity compared to controls.
- Increased T lymphocyte apoptosis was observed in patients with a first episode of NS.
- Reduced GR activity correlated negatively with T lymphocyte apoptosis rate.
Conclusions:
- Reduced antioxidant defense in NS patients may contribute to increased T lymphocyte apoptosis.
- Oxidative stress is implicated in the immune abnormalities seen in nephrotic syndrome.
Abstract:
Nephrotic syndrome (NS) is accompanied, and probably caused by, abnormalities in T lymphocyte function. The aim of this study was to investigate the antioxidant status of children with NS and its influence on the apoptosis of T cells. Fifty-seven children with NS were studied, aged 4-16 years (mean 7.4 years), 34 with a first episode (group I) and 23 in remission (>6 months) of NS (group II). The control group comprised 26 healthy children matched for age. Annexin V-FITC was used as a sensitive probe for identifying cells undergoing apoptosis. We found that apoptotic T lymphocytes occurred more frequently in patients with a first episode of NS than in children in remission and in the controls. In group I, total antioxidant status (TAS, plasma) was significantly reduced compared with controls (0.77+/-0.14 vs. 1.18+/-0.42 mmol/l, P<0.001). In group I children, glutathione reductase (GR, red blood cells) and glutathione peroxidase (GPX, red blood cells) activity was lower than in controls (GR 8.10+/-2.40 vs.10.55+/-3.81 U/g Hb, P<0.001) (GPX 28.65+/-6.99 vs. 33.84+/-13.11 U/g Hb, P=0.010). TAS levels and GR activity in group II were also lower than in the controls. A negative correlation between GR activity and the apoptosis rate of T lymphocytes was found. We conclude that in patients with NS, reduced antioxidant defense may contribute to an increase in the apoptosis rate of circulating lymphocytes.