الفهرس 
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Abstract
The aim of the present investigation was to study the effect of quercetin treatment on renal functions, vascular endothelium and some haemodynamic parameters and the underlying possible mechanisms in hyperuricemic rats. One hundred adult male albino rats weighing 150-200 grams, each, were used in this investigation. Rats were divided into the following groups: I- Non hyperuricemic group (20 rats): Rats with normal serum uric acid level (0.5 to 1.4 mg/dl) were selected in this group. Each rat was given 1ml of 0.9% saline (vehicle of potassium oxonate) daily by intraperitoneal (i.p) injection for 8 weeks.
II- Hyperuricemic non-treated group (20 rats): In this group each rat was injected by potassium oxonate (PO), uricase inhibitor, dissolved in 0.9% saline solution intraperitoneally in a dose of 250 mg/Kg daily for 4 weeks. Rats with serum uric acid level above 1.4 mg/dl were considered to be hyperuricemic. Rats were left for another additional four weeks under PO administration.
III- Hyperuricemic allopurinol-treated group (20 rats): In this group rats were rendered hyperuricemic as in the previous group. They were given allopurinol 5mg/kg dissolved in normal saline intragastrically daily starting from the fifth week of the experiment for 4 weeks.
IV- Hyperuricemic quercetin-treated group (20 rats): In this group rats were rendered hyperuricemic as in group II. They were given quercetin 50 mg/kg as suspension in distilled water intragastrically daily starting from the fifth week of the experiment for 4 weeks
V- Hyperuricemic combined allopurinol & quercetin-treated group (20 rats): In this group rats were rendered hyperuricemic as in group II. They were given combined treatement of allopurinol (5mg/kg) and quercetin (50mg/kg) administered intragastrically daily starting from the fifth week of the experiment for 4 weeks.
At the end of experimental period, 24h urine samples were collected for measurement of urine volume, proteins content and creatinine concentration to calculate creatinine clearance. Then, fasting retro-orbital blood samples were taken for estimation of serum levels of the following parameters: uric acid, creatinine, urea, TNFα, MDA and TAC. Then, 10 rats from each group were used for measurement of renal blood flow velocity and renal vascular resistance, invasive blood pressure and in vivo vascular reactivity of aorta to AngII, NE, SNP and Ach. The other 10 rats from each group were used for measurement of in vitro vascular reactivity after opening thoracic cage and isolation of thoracic aortae using isolated rat aortic ring technique. Also, isolated aortae were used for histopathological and immunohistochemical examination for assessment of vascular endothelial function using eNOS antibody.
In the present investigation, administration of potassium oxonate (PO), uricase inhibitor caused hyperuricemia with significant rise of serum uric acid, serum creatinine, serum urea, 24h urinary proteins serum TNFα, serum MDA, ABP, vascular reactivity of aorta to AngII and NE and significant reduction of creatinine clearance, serum TAC, renal blood flow velocity, and vascular reactivity to SNP and Ach when compared to the corresponding values in non hyperuricemic group.
Allopurinol treatement to hyperuricemic rats caused statistical significant reduction of serum uric acid, serum creatinine, serum urea, urinary proteins, serum MDA, serum TNFα, mABP, renal vascular resistance, vascular reactivity to AngII and NE; but caused significant elevation of creatinine clearance, serum TAC, renal blood flow velocity, vascular reactivity to SNP and Ach, when compared to the corresponding values in hyperuricemic non-treated group.
Treatment of hyperuricemic rats with quercetin revealed statistical significant reduction of serum uric acid, creatinine, urea, TNFα, MDA, urinary proteins, mABP, renal vascular resistance and vascular reactivity to AngII and NE and significant elevation of creatinine clearance, serum TAC, renal blood flow velocity, and percent of relaxation to SNP and Ach, when compared to the corresponding values in hyperuricemic non-treated group.
Combined treatment of hyperuricemic rats with allopurinol & quercetin revealed statistical significant reduction of serum uric acid, creatinine, urea, TNFα, MDA, urine protein, mABP, renal vascular resistance and vascular reactivity to AngII and NE; but caused significant elevation of creatinine clearance, serum TAC, renal blood flow velocity and vascular reactivity to Ach and SNP when compared to the corresponding values in hyperuricemic non-treated, hyperuricemic allopurinol-treated and hyperuricemic quercetin treated groups.
Quercetin controlled hyperuricemia and improved renal functions, vascular endothelial functions and hemodynamic parameters in hyperuricemic rats. Quercetin when combined with allopurinol resulted in more improvement in hyperuricemia, renal functions, vascular endothelial functions and hemodynamic parameters than allopurinol alone. This may be attributed to the multi-protective functions of quercetin treatement among which its hypouricemic, antioxidant and anti-inflammatory effects.