| Texto completo | |
| Autor(es): |
Tessaro, Helena Mendonca
;
Zambom, Fernanda Florencia Fregnan
;
Foresto-Neto, Orestes
;
Ribeiro, Sara Cristina Fim
;
de Sena, Claudia Ramos
;
Malheiros, Denise Maria Avancini Costa
;
Camara, Niels Olsen Saraiva
;
Fujihara, Clarice Kazue
;
Zatz, Roberto
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Gerontology; v. N/A, p. 13-pg., 2024-11-27. |
| Resumo | |
Introduction: The pathogenesis of aging nephropathy (AN) is yet to be elucidated. Intrarenal angiotensin II (AngII) and activation of the nuclear factor-kappa B (NF-kappa B) and NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathways exert a relevant pathogenic role in the progression of chronic kidney disease. We sought to investigate whether monotherapy with losartan and combined treatment with losartan and the NF-kappa B inhibitor pyrrolidine dithiocarbamate (PDTC) would attenuate experimental AN. Materials and Methods: Forty adult male Munich-Wistar rats were distributed among four groups: 12M (n = 10), untreated 12-month-old rats; 15M (n = 10), untreated 15-month-old rats; 15M(Los) (n = 8), rats receiving losartan (50 mg/kg/d); and 15M(Los+PDTC) (n = 8), rats receiving losartan and PDTC (60 mg/kg/d). All treatments were given by mouth from 12 to 15 months of age. Results: Group 15M exhibited slightly decreased tail-cuff pressure and marked increase in albuminuria, sclerotic glomeruli, cortical collagen-1 deposition and infiltration by myofibroblasts, AngII-positive cells, and proinflammatory M1 macrophages, whereas the amount of anti-inflammatory M2 macrophages was reduced. In addition, the renal abundance of TLR4, nuclear p65, and IL-6 was increased, indicating activation of the NF-kappa B pathway, without evidence of simultaneous activation of the NLRP3 cascade. Losartan treatment decreased cortical collagen-1 deposition, myofibroblasts, and AngII-positive cells and partially restored renal M2 but had no significant effect on albuminuria, glomerulosclerosis, or NF-kappa B activation. Combined losartan+PDTC prevented all the observed abnormalities. Discussion: Simultaneous blockade of renal AngII and inhibition of the NF-kappa B pathway may represent a novel alternative to limit the decline of renal function with age. (AU) | |
| Processo FAPESP: | 12/10926-5 - Patogênese e terapêutica da doença renal crônica: papel da imunidade inata na lesão de glomérulos, túbulos e interstício |
| Beneficiário: | Roberto Zatz |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |