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Titolo:
Radiation-induced kidney injury: a role for chronic oxidative stress?
Autore:
Robbins, MEC; Zhao, WL; Davis, CS; Toyokuni, S; Bonsib, SM;
Indirizzi:
Univ Iowa, Dept Radiol, Free Radical & Radiat Biol Program, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 at Biol Program, Iowa City, IA 52242 USA Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA Univ Iowa Iowa City IA USA 52242 a, Dept Biostat, Iowa City, IA 52242 USA Kyoto Univ, Dept Pathol & Biol Dis, Kyoto 6068501, Japan Kyoto Univ Kyoto Japan 6068501 t Pathol & Biol Dis, Kyoto 6068501, Japan Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 Dept Pathol, Augusta, GA 30912 USA
Titolo Testata:
MICRON
fascicolo: 2, volume: 33, anno: 2002,
pagine: 133 - 141
SICI:
0968-4328(2002)33:2<133:RKIARF>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
MARROW TRANSPLANT NEPHROPATHY; MESANGIAL CELLS; SUPEROXIDE-DISMUTASE; ANTIOXIDANT ENZYMES; EPITHELIAL-CELLS; FIBROSIS; IRRADIATION; NEPHRITIS; 8-HYDROXYDEOXYGUANOSINE; PREVENTION;
Keywords:
kidney irradiation; radiation nephropathy; 8-OHdG; DNA oxidation; oxidative stress; fibrosis;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Robbins, MEC Univ Iowa, Dept Radiol, Free Radical & Radiat Biol Program, B-180 ML, IowaCity, IA 52242 USA Univ Iowa B-180 ML Iowa City IA USA 52242 aCity, IA 52242 USA
Citazione:
M.E.C. Robbins et al., "Radiation-induced kidney injury: a role for chronic oxidative stress?", MICRON, 33(2), 2002, pp. 133-141

Abstract

Kidney irradiation clearly leads to a progressive reduction in function associated with concomitant glomerulo sclerosis and/or tubulointerstitial fibrosis. However, the particular cell types, mediators and/or mechanisms involved in the development and progression of radiation nephropathy remain illdefined. Angiotensin II (Ang II) plays a major pathogenic role; administration of Ang II blockers markedly abrogates the severity of radiation nephropathy in experimental models. Both ionizing radiation and Ang II signal viageneration of reactive oxygen species (ROS). Thus, we hypothesized that localized kidney irradiation might lead to a chronic oxidative stress. In view of the difficulty in measuring ROS in vivo we adopted an indirect immunohistochemical approach in which we used a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), one of the most commonly used markers of DNA oxidation. The right kidney of 7-8 week-old male Sprague-Dawley rats was removed. Five to 6 weeks later the remaining hypertrophied kidney was irradiated with single doses of 0-20.0 Gy X-rays. Groups of rats, three per dose, were killed at 4, 8, 16 and 24 weeks post-irradiation, their kidneys fixed, and sections stained with the 8-OHdG-specific antibody N45. 1.For quantitation of glomerular DNA oxidation with the N45.1 antibody stained sections, 50 glomeruli/animal were counted. The presence of any intensely stained nuclei withinthe glomerular tuft was scored as positive. Quantitation of tubular DNA oxidation employed a 10 X 10 point ocular arid. Sections were examined at 400magnification; 250 tubular profiles were counted. All tubules with any nuclear staining were scored as positive. Sham-irradiated kidneys showed little evidence of DNA oxidation over the experimental period. In contrast, localized kidney irradiation led to a marked, dose-independent increase in glomerular and tubular cell nuclear DNA oxidation. This increase was evident at the first time point studied, i.e. 4 weeks after irradiation, and persisted for up to 24 weeks postirradiation. DNA oxidation in the irradiated kidney was only seen in apparently viable glomerular and tubular cells. Thus, while from 16 to 24 weeks post-irradiation structural alterations had progressed to glomerular sclerosis and tubular atrophy, positive staining for 8-OHdG was not observed in severely atrophic tubules. Similarly, fewer positive staining cells were noted in glomeruli undergoing sclerosis, while none were seen in totally sclerotic glomeruli. These data support the hypothesis that renal irradiation is associated with a chronic and persistent oxidative stress. (C) 2001 Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/09/20 alle ore 12:47:00