Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis

Abstract

BackgroundCatalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model.MethodsADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) and control wild-type mice (C3H/AnLCsaCsa). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups.ResultsThe ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation.ConclusionsThese data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.

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

“…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 ]. Albuminuria and lipid peroxidation have also been associated with kidney damage in doxorubicin-induced NS [ 10 ]. The results of the present study reveal peaks in urinary albumin excretion and MDA production seven days after doxorubicin injection, suggesting the possible involvement of ROS in the initial change in the glomerular filtration membrane.…”

“…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 ].…”

“…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 ].…”

Podocyte autophagy is associated with foot process effacement and proteinuria in patients with minimal change nephrotic syndrome

“…A quantitative examination was carried out to count the number of podocyte foot processes per 10 μm of glomerular basement membrane (GBM) in each glomerulus. The mean number of podocyte foot processes was determined as the FPE score, as described previously [39,40]. Representative electron micrographs used for the evaluation of the podocyte FPE score are shown in S1 Fig.…”

Pathophysiology and treatment of focal segmental glomerulosclerosis: the role of animal models

“…Studies that will be discussed used male Munich-Wister rats and injected a single dose. The given doses range from 1,5 to 5 mg/kg in rats [49,50] and 10 to 15 mg/kg in mice [51]. It is important to test the dose before conducting experiments since adriamycin has a small pharmaceutical range, outside of which it becomes toxic.…”