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

Keiichi Takiue,Yoko Kikumoto,Da-Hong Wang,Hirofumi Makino,Hitoshi Sugiyama,Keiki Ogino,Shinji Kitamura,Tatsuyuki Inoue,Yohei Maeshima,Masashi Kitagawa,Noriyoshi Masuoka,Hiroshi Morinaga

doi:10.1186/1471-2369-13-14

Keiichi Takiue, Yoko Kikumoto + Show 10 more

Open Access

https://doi.org/10.1186/1471-2369-13-14

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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.

Highlights

Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals
Chen et al [9] reported that BALB/c mice were susceptible to renal toxicity arising from the administration of the anthracycline antibiotic, adriamycin (ADR), with selective injury to podocytes resulting in severe proteinuria and progressive renal failure [9,10]
Kidney weight, and heart weight in the mouse ADR nephropathy model The ADR nephropathy model has been extensively studied in animals of the BALB/c background

Summary

Introduction

Catalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. Chen et al [9] reported that BALB/c mice were susceptible to renal toxicity arising from the administration of the anthracycline antibiotic, adriamycin (ADR), with selective injury to podocytes resulting in severe proteinuria and progressive renal failure [9,10]. This was described as the first experimental model of FSGS in mice. The activities of antioxidant enzymes including catalase, GPX and Mn-SOD and the glutathione concentration in renal cortex were decreased by ADR nephropathy in BALB/c mice [11]. The administration of the soluble receptor for advanced glycation endproducts (AGEs) suppressed AGE generation and reactive oxygen species in the ADR nephropathy mice [13]

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