Biomarkers of oxidative damage and antioxidant enzyme activities in pre-dialysis Balkan endemic nephropathy patients

To obtain more insight into molecular mechanisms underlying oxidative stress in Balkan endemic nephropathy (BEN), biomarkers of oxidative stress and antioxidant enzyme activities were studied in 38 pre-dialysis BEN patients, 21 healthy BEN family members and 36 healthy subjects from non-endemic areas. Protein thiol groups (P-SH), antioxidant enzyme activities [superoxide dismutase (SOD) and glutathione peroxidase (GPX)], were determined in plasma spectrophotometrically, while malondialdehyde adducts (MDA) by enzyme immunoassay. BEN patients had significantly lower plasma GPX activity in comparison with values for both control groups (p = 0.016), gradually decreasing with kidney function impairment estimated by glomerular filtration rate (r = 0.53, p = 0.002). GPX activity was inversely correlated with serum urea (r = -0.627, p < 0.001), creatinine (r = -0.53, p < 0.05), urinary excretion of protein and alpha(1)-microglobulin (r = -0.44, p = 0.012; r = -0.50, p < 0.007). Significant upregulation of SOD activity was observed in healthy BEN family members (p < 0.05). While the concentration of MDA adducts was similar in all three groups, BEN patients and healthy BEN family members exhibited increased protein damage, based on fewer P-SH groups in comparison with subjects from non-BEN areas (p = 0.085; p = 0.014, respectively). Based on our results on increased oxidative protein damage in both pre-dialysis BEN patients and healthy BEN family members, it can be speculated that individuals from BEN areas, in general, are chronically exposed to some prooxidant environmental compounds. Moreover, decrease in plasma GPX activity, as a consequence of impaired kidney function, could further affect oxidative status in BEN patients.