Dietary quercetin augments activator protein-1 and does not reduce nuclear factor-kappa B in the renal cortex of rats with established chronic glomerular disease.
OBJECTIVE
Quercetin, a naturally occurring dietary flavonoid, is a potent in vitro inhibitor of the transcription factors, nuclear factor (NF)-kappa B and activator protein (AP)-1. Here we investigated the efficacy of quercetin to suppress renal cortical NF-kappa B/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-kappa B 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).


CONCLUSIONS
These data suggest that supplementation of the diet with quercetin is not an effective therapeutic strategy alone to reduce NF-kappa B/ AP-1 activation in chronic glomerular diseases, and paradoxically could be associated with adverse renal effects.
Rangan
Gopala K
GK
Department of Renal Medicine, University of Sydney at Westmead Hospital, Westmead, Sydney, Australia. gopala.rangan@health.wa.gov.au
Wang
Yiping
Y
Harris
David C H
DC
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D002908:Chronic Disease; D004032:Diet; D004317:Doxorubicin / Q000633:toxicity; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D007672:Kidney Cortex / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011794:Quercetin / Q000008:administration & dosage* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D004317:Doxorubicin; D011794:Quercetin