Quercetin Treatment Improves Renal Function and Protects the Kidney in a Rat Model of Adenine-Induced Chronic Kidney Disease

Abstract

BACKGROUND The aim of this study was to examine the effects of the natural flavonoid, quercetin, in a rat model of adenine-induced chronic kidney disease. MATERIAL AND METHODS Forty male Wister rats were divided into four groups: normal (no adenine or quercetin) (n=10); untreated model (treated withadenine but not quercetin) (n=10); quercetin-treated model (5 mg/kg/day for 21 days) (n=10); quercetin-treated model (10 mg/kg/day for 21 days) (n=10). Urine and blood samples were collected and rat kidneys were examined histologically. RESULTS Comparison of the findings of the model rats treated with quercetin (n=20) with non-treated model rats (n=10) showed reduced levels of fibroblast growth factor 23 (FGF23): normal group, 19.6 pg/ml; untreated group, 73.6 pg/ml; quercetin-treated group (5 mg/kg), 34.25 pg/ml; and quercetin-treated group (10 mg/kg), 21.3 pg/ml. Quercetin-treated model rats had reduced serum levels of parathyroid hormone (PTH), inorganic phosphate, increased urine protein-to-creatinine ratio, increased urine antioxidants, serum lactate dehydrogenase (LDH), and interleukin (IL)-8 when compared with the untreated model group and the control group. Quercetin treatment 10 mg/kg (n=10) reduced the levels of creatinine, blood urea nitrogen (BUN), and urinary uric acid. Renal histopathology in model rats treated with quercetin (n=20) showed reduced inflammation compared with the untreated model rats (n=10). CONCLUSIONS In a rat model of adenine-induced chronic kidney disease, treatment with quercetin improved renal function, reduced oxidative stress factors, serum levels of FGF23, and kidney inflammation.

Figure 1

Quercetin treatment for 21 days inhibited the expression of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and inorganic phosphate in the adenine-induced chronic kidney disease rat model. The rats were treated with 5 mg/kg (n=10) and 10 mg/kg (n=10) doses of quercetin for 21 days, whereas the normal (n=10) and untreated model rats (n=10) were given equal volume of normal saline. Values of *** P<0.0001 represent significant differences between the untreated group compared with the normal group. Values of ^# P<0.01, and ^## P<0.001 represent significant differences between the untreated group compared with the treated group.

Figure 2

Quercetin treatment on day 22 reduced the values of the urine protein-to-creatinine ratio and urine uric acid in the adenine-induced chronic kidney disease rat model. The urine samples of the rats were collected over 24 hours on day 22 of the treatment and the values of rhe urine protein-to-creatinine ratio and uric acid were determined. Values of *** P<0.0001 represent significant differences between the untreated group compared with the normal group. Values of ^# P<0.01 and, ^### P<0.0001 represent significant differences between the untreated group compared with the treated group.

Figure 3

Quercetin treatment reduced the levels of creatinine and blood urea nitrogen (BUN) in the serum of the adenine-induced chronic kidney disease rat model. The blood samples from the rats were collected after the completion of treatment, centrifuged and then analyzed to measure the levels of creatinine and blood urea nitrogen (BUN). Values of *** P<0.0001 represent significant differences between the untreated group compared with the normal group. Values of ^# P<0.01 and ^## P<0.001 represent significant differences between the untreated group compared with the treated group.

Figure 4

Effect of quercetin on (A) urinary antioxidants, (B) lactate dehydrogenase (LDH) activity, and (C) urine interleukin (IL)-6 concentrations, in the adenine-induced chronic kidney disease rat model. All experiments were performed in triplicate and presented as the mean ± standard deviation (SD). Values of ** P<0.001, and *** P<0.0001 represent significant differences between the untreated group compared with the normal group. Values of ^# P<0.01, ^## P<0.001, and ^### P<0.0001 represent significant differences between the untreated group compared with the treated group.

Figure 5

Photomicrographs showing the histological changes in the kidney, including the renal tubules, in the adenine-induced chronic kidney disease rat model. The kidneys of the euthanized rats in the study were removed after the completion of treatment. Renal tissue sections were prepared and histochemically stained with hematoxylin and eosin (H&E). Magnification, ×200.