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

Edilia Tapia, Dolores J. Sánchez-González, Omar N. Medina-Campos, Virgilia Soto, Carmen Ávila-Casado, Claudia M. Martínez-Martínez, Richard J. Johnson, Bernardo Rodríguez-Iturbe, José Pedraza-Chaverrí, Martha Franco, Laura Gabriela Sánchez-Lozada

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

15 Citas (Scopus)

Resumen

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

Idioma originalInglés
Páginas (desde-hasta)F1431-F1439
PublicaciónAmerican Journal of Physiology - Renal Physiology
Volumen295
N.º5
DOI
EstadoPublicada - nov 2008
Publicado de forma externa

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