Selected markers of oxidative stress in rats with active Heymann nephritis

Reactive oxygen species play an important role in the pathogenesis of different glomerulopathies. The purpose of this study was to examine selected markers of oxidative stress and antioxidant defense in active Heymann nephritis (AHN), which is a model of human membranous nephropathy.

AHN was induced in female Wistar rats by i.p. injection of proximal tubule brush border antigen (Fx1A). The control animals received an equivolume injection of saline. The animals were sacrificed at 6, 9, 15, 17, 18, 19, 22 and 23 weeks after Fx1A administration. We assayed the plasma concentration of thiobarbituric acid-reactive substances (TBARS) and nitric oxide metabolites (nitrites + nitrates, NOx) as well as total plasma antioxidant capacity (ferric reducing ability of plasma, FRAP) and serum paraoxonase (PON) activity.

Fx1A-injected rats demonstrated a marked increase in proteinuria and impairment of renal excretory function evidenced by increased plasma creatinine and uric acid. Histologically, diffuse renal changes were seen, characterized by glomerular hypercellularity, increased glomerular size and narrowing of Bowman's space. Ultrastructural studies revealed diffuse fusion of foot processes and detachment of podocytes, subepithelial immune deposits in the glomerular capillary wall, thickening of the glomerular basement membrane, and local accumulation of lymphocytes and macrophages in glomeruli and interstitial cells. In the AHN group, TBARS increased significantly beginning in the 9th week, reaching maximum at the 23rd week (139.4% of time-matched control). The plasma concentration of NOx demonstrated a biphasic increase. The first peak (249.9% of control) was observed at the 9th week, followed by a decrease to normal between the 17th and 19th week. Then the NOx concentration increased to 211% of control at the 23rd week. FRAP began to increase in the 9th week and reached its maximum (134.9% of control) at the 15th week. After the 18th week FRAP returned progressively to control levels. PON activity was 17.0%, 19.1% and 21.3% lower in AHN than in the control group at the 19th, 22nd, and 23rd weeks, respectively.

These results indicate that AHN is associated with oxidant-antioxidant imbalance, which may contribute to renal damage in this model of glomerulonephritis.