American Journal of Physiology - Renal Physiology, 2008-11, Vol.295 (5), p.F1431-F1439
2008
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- Autor(en) / Beteiligte
- Titel
- Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria
- Ist Teil von
- American Journal of Physiology - Renal Physiology, 2008-11, Vol.295 (5), p.F1431-F1439
- Ort / Verlag
- United States: American Physiological Society
- Erscheinungsjahr
- 2008
- Quelle
- Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals
- Beschreibungen/Notizen
- We evaluated whether the blockade of the proinflammatory transcription factor NF-kappaB would modify the oxidative stress, inflammation, and structural and hemodynamic alterations found in the kidney as a result of massive proteinuria. Twenty male Sprague-Dawley rats were injected with 2 g of BSA intraperitoneally daily for 2 wk. Ten of them received in addition the inhibitor of NF-kappaB activation pyrrolidine dithiocarbamate (PDTC; 200 mg.kg(-1).day(-1) sc) and the rest received vehicle. Seven rats that received intraperitoneal saline were used as controls. Glomerular hemodynamics were studied after 14 days. Markers of oxidative stress (NF-kappaB subunit p65+ cells, 3-nitrotyrosine, and 4-hydroxynonenal), inflammation (cortical CD68+ cells and NOS-II), and afferent arteriole damage were assessed by immunohistochemistry and morphometry. Activity of antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase was evaluated in renal cortex and medulla. Albumin overload induced massive proteinuria, oxidative stress with reduced activity of antioxidant enzymes, NF-kappaB activation, inflammatory cell infiltration, a significant presence of proteinaceous casts, systemic and glomerular hypertension, as well as arteriolar remodeling. Treatment with PDTC prevented or improved all of these findings. In this model of nephrotic syndrome, we demonstrate a key role for oxidative stress and inflammation in causing systemic and glomerular hypertension and proteinuria. Oxidative stress and inflammation may have a key role in accelerating renal injury associated with intense proteinuria.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1931-857X, 0363-6127eISSN: 1522-1466DOI: 10.1152/ajprenal.90201.2008Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2584905
- Format
- –
- Schlagworte
- Aldehydes - metabolism, Animals, Antigens, CD - metabolism, Antigens, Differentiation, Myelomonocytic - metabolism, Blood Pressure - drug effects, Cells, Glomerular Filtration Rate - drug effects, Glomerular Filtration Rate - physiology, Glutathione Reductase - metabolism, Hypertension, Renal - drug therapy, Hypertension, Renal - physiopathology, Kidney - drug effects, Kidney - metabolism, Kidney - physiopathology, Kidney Glomerulus - drug effects, Kidney Glomerulus - physiopathology, Kidneys, Male, Nitric Oxide Synthase Type II - metabolism, Organ Size - drug effects, Oxidation, Oxidative Stress - drug effects, Peroxidases - metabolism, Proteins, Proteinuria - drug therapy, Proteinuria - physiopathology, Pyrrolidines - pharmacology, Pyrrolidines - therapeutic use, Rats, Rats, Sprague-Dawley, Renal Plasma Flow - drug effects, Renal Plasma Flow - physiology, Rodents, Superoxide Dismutase - metabolism, Thiocarbamates - pharmacology, Thiocarbamates - therapeutic use, Transcription Factor RelA - metabolism, Tyrosine - analogs & derivatives, Tyrosine - metabolism