Chronic inhibition of nuclear factor kappa B attenuates aldosterone/salt-induced renal injury

Aims: Recent studies suggested that nuclear factor kappa B (NF-kappa B) plays a key role in the pathogenesis of renal injury. This study investigated whether NF-kappa B inhibition attenuates progressive renal damage in aldosterone/salt-induced renal injury and its mechanisms. Main methods: Adult male rats were uninephrectomized and treated with one of the following for 4 weeks: vehicle (0.5% ethanol, subcutaneously): vehicle/1% NaCl (1% NaCl in drinking solution); aldosterone/1% NaCl (1% NaCl in drinking solution and aldosterone, 0.75 mu g/h, subcutaneously); or aldosterone/1%NaCl + pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappa B (100 mg/kg/day, by gavage). The activity of NF-kappa B was measured by EMSA and immunohistochemistry, CTGF and ICAM-1 were measured by Western blot and real-time PCR, and TGF-beta and CTGF were measured by immunohistochemistry. Key findings: Rats that received aldosterone/1% NaCl exhibited hypertension and severe renal injury. Renal cortical mRNA levels of CTGF, TGF-beta, ICAM-1 and collagen IV, protein expression of CTGF and ICAM-1, and NF-kappa B-DNA binding activity were significantly upregulated in rats that received aldosterone/1% NaCl. Treatment with PDTC significantly decreased the percentage of cells positive for CTGF and TGF-beta; mRNA levels of CTGF, TGF-beta, ICAM-1 and collagen IV, and protein levels of CTGF and ICAM-1 were also inhibited by PDTC. Significance: These data suggest that the NF-kappa B signal pathway plays a role in the progression of aldosterone/salt-induced renal injury. (c) 2012 Elsevier Inc. All rights reserved.