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Open Access Research article

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

Keiichi Takiue1, Hitoshi Sugiyama2*, Tatsuyuki Inoue13, Hiroshi Morinaga2, Yoko Kikumoto1, Masashi Kitagawa1, Shinji Kitamura1, Yohei Maeshima1, Da-Hong Wang4, Noriyoshi Masuoka5, Keiki Ogino4 and Hirofumi Makino1

Author Affiliations

1 Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

2 Center for CKD and Peritoneal Dialysis, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

3 Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan

4 Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

5 Department of Life Science, Okayama University of Science, 1-1, Ridai-cho, Kita-ku, Okayama 700-0005, Japan

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BMC Nephrology 2012, 13:14  doi:10.1186/1471-2369-13-14

Published: 25 March 2012

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/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.

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.