Dietary Quercetin Augments Activator Protein-1 and Does Not Reduce Nuclear Factor-kappaB in the Renal Cortex of Rats with Established Chronic Glomerular Disease.

摘要

Background/Aims: Quercetin, a naturally occurring dietary flavonoid, is a potent in vitro inhibitor of the transcription factors, nuclear factor (NF)-kappaB and activator protein (AP)-1. Here we investigated the efficacy of quercetin to suppress renal cortical NF-kappaB/AP-1 activation and tubulointerstitial injury, in vivo, in a nephrotic rat model of chronic glomerular disease. Methods: Adult male Wistar rats with (n = 27) or without (n = 15) Adriamycin nephropathy (AN) were stratified into six groups (according to proteinuria and endogenous creatinine clearance, measured on day 10) and pair-fed a semipurified diet supplemented with or without quercetin (0.5, 2%) from day 14 to 36. Results: Quercetin-fed rats had minimal weight gain during the study (p < 0.05). In AN, proteinuria, the decline in endogenous creatinine clearance, hypercholesterolaemia and cortical tubulointerstitial injury were not reduced by quercetin. Quercetin had no effect on renal cortical NF-kappaB activation, but unexpectedly exacerbated the induction of AP-1 in AN (by 67%, p < 0.05). In normal rats, quercetin increased proteinuria (by 75%, p < 0.05), renal cortical AP-1 activation (by 198%, p = 0.06), and malondialdehyde production (by 110%, p < 0.05). Conclusion: These data suggest that supplementation of the diet with quercetin is not an effective therapeutic strategy alone to reduce NF-kappaB/ AP-1 activation in chronic glomerular diseases, and paradoxically could be associated with adverse renal effects.