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

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

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11 Citations (Scopus)

Abstract

Background: Catalase 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. Methods. ADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCs bCs b) and control wild-type mice (C3H/AnLCs aCs a). 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. Results: The 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. Conclusions: These data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.

Original languageEnglish
Article number14
JournalBMC nephrology
Volume13
Issue number1
DOIs
Publication statusPublished - 2012

ASJC Scopus subject areas

  • Nephrology

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