NF-kappa B blockade during short-term L-NAME and salt overload strongly attenuates the late development of chronic kidney disease

Autor(es)

Oliveira, Karin Carneiro ^[1] ; Fregnan Zambom, Fernanda Florencia ^[1] ; Albino, Amanda Helen ^[1] ; Alarcon Arias, Simone Costa ^[1] ; Avila, Victor Ferreira ^[1] ; Faustino, Viviane Dias ^[1] ; Avancini Costa Malheiros, Denise Maria ^[1] ; Saraiva Camara, Niels Olsen ^{[2, 1]} ; Fujihara, Clarice Kazue ^[1] ; Zatz, Roberto ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Clin Med, Renal Div, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Lab Transplantat Immunobiol, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY; v. 319, n. 2, p. F215-F228, AUG 2020.
• Citações Web of Science: 0

Resumo

Nitric oxide synthase inhibition by N-omega-nitro-L-arginine methyl ester (L-NAME) plus a high-salt diet (HS) is a model of chronic kidney disease (CKD) characterized by marked hypertension and renal injury. With cessation of treatment, most of these changes subside, but progressive renal injury develops, associated with persistent low-grade renal inflammation. We investigated whether innate immunity. and in particular the NF-kappa B system, is involved in this process. Male Munich-Wistar rats received HS + L-NAME (32 mg.kg(-1).day(-1)), whereas control rats received HS only. Treatment was ceased after week 4 when 30 rats were studied. Additional rats were studied at week 8 (n = 30) and week 28 (n = 30). As expected, HS + L-NAME promoted severe hypertension, albuminuria, and renal injury after 4 wk of treatment, whereas innate immunity activation was evident. After discontinuation of treatments, partial regression of renal injury and inflammation occurred, along with persistence of innate immunity activation at week 8. At week 28, glomerular injury worsened, while renal inflammation persisted and renal innate immunity remained activated. Temporary administration of the NF-kappa B inhibitor pyrrolidine dithiocarbamate, in concomitancy with the early 4-wk HS + L-NAME treatment, prevented the development of late renal injury and inflammation, an effect that lasted until the end of the study. Early activation of innate immunity may be crucial to the initiation of renal injury in the HS + L-NAME model and to the autonomous progression of chronic nephropathy even after cessation of the original insult. This behavior may be common to other conditions leading to CKD. (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
• Processo FAPESP: 15/08253-0 - Papel da imunidade inata na doença renal crônica que se segue à recuperação da nefropatia induzida pela inibição temporária do óxido nítrico associada a uma sobrecarga salina
• Beneficiário: Karin Carneiro de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto