Tumour necrosis factor α, lipid peroxidation and NO^• are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome

Abstract

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2⋅-, H₂O₂ and OH^• causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-α and NO^• react with O2⋅- and cause further antioxidant depletion with an increase in mutation frequency by H₂O₂. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-α, NO^• and LPO in patients with WMS.Methods: A group of 10 WMS patients (four males, six females; age, 26.5±19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3±18.2 years) were included. Serum TNF-α levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO^• levels were evaluated by Griess reaction.Results: Mean levels of TNF-α (8.3±0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3±0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4±0.8 and 1.8±0.6 μmol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9±626.6 versus 5261.6±523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4±49.3 versus 713.4±55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7±42.0 versus 756.5±47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3±15.0 versus 131.4±19.7 U/g protein, p=0.0113). In addition, serum NO^• ((NO2−+NO3−)) levels were also significantly (p=0.0002) increased in WMS patients (54.4±5.7 versus 26.9±6.7 μmol/l). RBC-CAT levels were similar between groups (125.6±21.3 versus 131.0±21.5 k/g Hb, p=0.8798).Conclusions: The elevated LPO, TNF-α and NO^• with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.