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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/F1431    most recent 90201.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Tapia, E. Articles by Sánchez-Lozada, L. G. Search for Related Content PubMed PubMed Citation Articles by Tapia, E. Articles by Sánchez-Lozada, L. G.

Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria

Departments of ¹Nephrology and ²Pathology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City; ³Nephrology, Hypertension and Transplantation, University of Florida, Gainesville, Florida; ⁴Department of Cell Biology, Escuela Médico Militar, México City; ⁵Servicio de Nefrología, Hospital Universitario and Universidad del Zulia, IVIC-Zulia, Maracaibo, Venezuela; and ⁶Facultad de Química, Universidad Nacional Autónoma de México, México City, México

Submitted 18 March 2008 ; accepted in final form 26 August 2008

We evaluated whether the blockade of the proinflammatory transcription factor NF-B 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-B 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-B 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-B 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.

preglomerular arteriolopathy; inflammatory cell infiltration; antioxidant enzymes