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Nephrol Dial Transplant. 2011 Nov;26(11):3484-95. doi: 10.1093/ndt/gfr195. Epub 2011 May 19.

Quercetin reduces cisplatin nephrotoxicity in rats without compromising its anti-tumour activity.

Author information

1
Unidad de Fisiopatología Renal y Cardiovascular, Departamento de Fisiología y Farmacologıía, Universidad de Salamanca, Salamanca, Spain.

Abstract

BACKGROUND:

Nephrotoxicity is the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Our aim was to investigate the protective effect of quercetin on cisplatin nephrotoxicity in a rat tumour model in vivo and to examine the mechanisms of renal protection.

METHODS:

Breast adenocarcinoma (13762 Mat B-III) cells were inoculated subcutaneously in male Fischer rats and 7 days later, the rats were administered daily with quercetin [50 mg/kg/day, intraperitoneally (i.p.)] or vehicle. Four days after that, the rats were given a single dose of cisplatin (4 mg/kg, i.p.) or vehicle. Tumour growth and renal function were monitored throughout the experiment. Two or 6 days after cisplatin administration, the rats were killed and the kidneys and tumours were removed to examine renal function and toxicity markers in both tissues.

RESULTS:

In the kidney, cisplatin treatment induced: (i) a decrease in renal blood flow and glomerular filtration rate, (ii) tubular necrosis/apoptosis, (iii) increased lipid peroxidation and decreased endogenous antioxidant systems, (iv) increased expression of inflammation markers and (v) increased activity of the apoptosis executioner caspase-3. Cisplatin effectively reduced tumour size and weight.

CONCLUSIONS:

Co-treatment with quercetin partially prevented all the renal effects of cisplatin, whereas it did not impair its anti-tumour activity. In conclusion, in a model of tumour-bearing rats, quercetin prevents the nephrotoxic effect of cisplatin without affecting its anti-tumour activity.

PMID:
21602180
DOI:
10.1093/ndt/gfr195
[Indexed for MEDLINE]

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