title: Increased oxidative stress in the mouse adriamycin model of glomerulosclerosis is accompanied by deposition of ferric iron and altered GGT activity in renal cortex.
abstract: Chronic renal failure evolves inevitable towards glomerular and tubulo-interstitial sclerosis. This pathological process involves a disturbed redox status of the kidney tissue, leading to irreversible damage. In this study we investigate in an adriamycin model of chronic renal failure in mice the evolution of in vivo hydrogen peroxide production, and the possible role of gamma-glutamyl transpeptidase and ferric iron in the process. Histological changes and ferric iron deposits are evaluated by histochemical staining. To evaluate oxidative stress residual catalase activity, TBARS formation and gamma-glutamyl transpeptidase activity are measured spectrophotometrically. While catalase activity remains the same, a decreased residual catalase activity indicates an increased formation of hydrogen peroxide. Both the activity of gamma-glutamyl transpeptidase and TBARS formation is increased at early stages of the disease. Ferric iron is clearly present in the proximal tubule. Twenty days after adriamycin injection all parameters decrease, probably due to the destruction of the tissue. Our data show the involvement of oxidative stress in the progression of adriamycin induced renal failure in mice. Both radical production and oxidative damage are measurable, while the altered activity of gamma-glutamyl transpeptidase and the deposition of ferric iron suggest the involvement of these factors in the development of a disturbed redox status in the kidney cortex.
authors.affiliation: Department of Human Anatomy, Academic Hospital of the Vrije Universiteit Brussel, Brussels, Belgium. bceyssen@vub.ac.be
authors.forename: Bart
authors.initials: B
authors.lastname: Ceyssens
authors.forename: Marina
authors.initials: M
authors.lastname: Pauwels
authors.forename: Bart
authors.initials: B
authors.lastname: Meulemans
authors.forename: Dierik
authors.initials: D
authors.lastname: Verbeelen
authors.forename: Christiane
authors.initials: C
authors.lastname: Van den Branden
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin; D005260:Female; D005290:Ferric Compounds / Q000378:metabolism*; D005923:Glomerulosclerosis, Focal Segmental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007672:Kidney Cortex / Q000201:enzymology; D007684:Kidney Tubules / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000502:physiology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
chemical_list: D005290:Ferric Compounds; D017392:Thiobarbituric Acid Reactive Substances; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D005723:gamma-Glutamyltransferase