title: Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis.
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(b)Cs(b)) and control wild-type mice (C3H/AnLCs(a)Cs(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.
authors.affiliation: Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Takiue
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sugiyama
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morinaga
authors.forename: Yoko
authors.initials: Y
authors.lastname: Kikumoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Kitamura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maeshima
authors.forename: Da-Hong
authors.initials: DH
authors.lastname: Wang
authors.forename: Noriyoshi
authors.initials: N
authors.lastname: Masuoka
authors.forename: Keiki
authors.initials: K
authors.lastname: Ogino
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
mesh_terms: D020642:Acatalasia / Q000150:complications / Q000503:physiopathology*; D000419:Albuminuria / Q000139:chemically induced* / Q000503:physiopathology*; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004198:Disease Susceptibility; D004317:Doxorubicin; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout
chemical_list: D004317:Doxorubicin; D002374:Catalase