Role of reactive oxygen species in pathogenesis of nephrotic syndrome

Abstract

Nephrotic syndrome is the common chronic disorder characterized by alteration of permeability of the glomerular capillary wall, resulting in its inability to restrict the urinary loss of proteins. Nephrotic syndrome is characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia associated with peripheral edema. The molecular basis of glomerular permselectivity remains largely unknown. In recent years it has been proposed that Nephrotic syndrome is a consequence of an imbalance between oxidant and antioxidant activity. The present study was aimed to test that the reactive oxygen species are the mediators of excessive protein permeability and other complications of Nephrotic syndrome. For this 30 adults with Nephrotic syndrome were studied. The control group comprised 30 healthy adults matched for age. Serum levels of lipid peroxides, nitric oxide (NO⊙), α- tocopherol, ascorbic acid, erythrocyte superoxide dismutase activity, serum albumin, uric acid, cholesterol and plasma total antioxidant capacity were measured. Student's 't' test was applied for statistical analysis. There was a significant increase in lipid peroxide (1.58 ± 0.42 in controls, 3.64 ±1.3 in patients) (P<0.001) levels in study group as compared with controls. α-tocopherol (12.95 ± 1.04 in controls, 9.93 ± 1.43 in patients) (P<0.001), erythrocyte SOD activity(1.88 ± 0.9 in controls 1.07 ± 0.5 in patients) (P=0.01), serum albumin(4.06 ± 0.50 in controls, 3.04 ± 0.11 in patients) (P<0.001), and plasma total antioxidant capacity (847.33 ± 126.83 in controls, 684.00±102.94 in patients) (P<0.001) were significantly decreased. There was non-significant increase in uric acid (P>0.05), a non-significant decrease in NO⊙ (38.48 ± 15.47 in controls 37.47 ± 14.27 in patients) (P>0.05) and ascorbic acid levels ascorbic acid,( 0.95 ± 0.31in controls 0.79 ± 0.30 in patients) (P>0.05) in study group as compared with controls. Imbalance between oxidants and antioxidants may contribute to pathogenesis of proteinuria and related complications in nephrotic syndrome.

Increased Migratory and Activation Cell Markers of Peripheral Blood Lymphocytes in an Experimental Model of Nephrotic Syndrome

“…The change in leukocyte activation and migration may influence the course of NS, with the possible participation of these cells in renal oxidative stress and albuminuria induction in the early stage of the disease. Human patients with NS exhibit increased ROS production in the plasma associated with a reduction in the amount of plasma albumin [ 9 ]. In an animal model of doxorubicin-induced NS, increased TBARS production has been found [ 8 ], associated with a reduction in the activity of catalase in renal tissue [ 11 ].…”

“…Kidney injury in INS may also be related to oxidative tissue damage through the increased production of reactive oxygen species (ROS) [ 8 – 10 ]. Recent studies have shown that patients with NS patients have higher levels of ROS than healthy controls [ 9 ]. Lipid peroxidation products have been associated with animal models of NS [ 8 , 10 , 11 ], while changes in the activity of superoxide dismutase (SOD) and catalase have been detected in the plasma of patients [ 9 ] and the renal tissue of animals with NS [ 10 , 11 ].…”

Antioxidant status of children with idiopathic nephrotic syndrome

“…Hence, it appears that SOD activity is not altered consistently in nephrotic syndrome. Also, whereas Ghodake et al [29] found unchanged ascorbic acid concentrations, other studies noted reduced levels in active disease compatible with consumption as part of antioxidant defense mechanisms [3,30]. Dwivedi and Sarkar [30] reported decreased levels of zinc during the active phase of nephrotic syndrome, with a significant increase following antioxidant treatment.…”

Serum levels of malondialdehyde, vitamin C and E in idiopathic nephrotic syndrome: a meta-analysis

“…Malonyldialdehyde (MDA), by-product of lipid peroxidation, is often tested to predict the status of ROS indirectly. 7,8 Also, the micronutrients including vitamin C and E are non-enzymatic antioxidants that will decline due to the consumption of oxidative stress. In this sense, it is reasonable to hypothesize that the alterations of MDA, vitamin C and E may be associated with INS.…”

“…To date, several studies [9][10][11][12][13][14][15][16] have showed the alterations of these parameters in the INS subjects. However, the relative small number of participants limited the statistical power, and some of the results were in conflict.…”