Abstract

ABSTRACT To study what kind of role uric acid play on the relationship between oxidative Stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats. Twenty-six eight male Wistar rats were divided into two groups randomly. Potassium oxonate was used to establish hyperuricemic model for four weeks. In 2nd and 4th week, uric acid (UA) level, total superoxide dismutase (T-SOD), Gu,Zn-SOD activity and interleukin-1beta (IL-1β) concentration in serum were determined respectively. In 4th week, one hour after last PO treatment, five rats of every group were given Evans Blue to test blood-brain barrier (BBB) permeability. Other brains were obtained to analysis T-SOD, Gu,Zn-SOD activity and IL-1β concentration in cerebral system. Meanwhile, brain and kidney were stained with hematoxylin and eosin (H&E) to observe pathological change. In 2nd week, both of T-SOD and Gu,Zn-SOD activity in serum increased obviously (P<0.05) in hyperuricemia rats. However, IL-1β content didn’t change remarkably. In the 4th week, T-SOD activity in model group had become similar with control group, and at the same time IL-1β content in serum increased significantly (P<0.05). Pathological section showed the structural and functional unit of the kidney had been damaged. On the contrary, both of T-SOD and Gu,Zn-SOD activity in brain increased obviously (P<0.05), but IL-1β concentration was no significant difference between two groups. In addition, the results of Evans Blue and H&E suggested the integrity of BBB and structure of brain were not changed after PO treatment. The permeability of BBB and form of UA would be potential factors to decide what kind role UA play on keeping balance between anti-oxidative stress and induction of inflammatory response.

Highlights

  • Uric acid (UA) is the end product of purine metabolism in humans

  • Compared with control rats injected with vehicle alone, potassium oxonate (PO) made serum uric acid (SUA) level significantly increased by 18.6% (P

  • Gu,Zn-super oxide dismutase (SOD) activity was 80.40±34.71 U/mL in control group and 117.91±23.71 U/mL in model group respectively(n=8).Compared with control group, high UA level increased both total superoxide dismutase (T-SOD) and Gu,Zn-SOD activity significantly (P

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Summary

Introduction

Uric acid (UA) is the end product of purine metabolism in humans. Owing to redundant UA deposition, tissue injury triggers innate responses and early phases of host defence, and promotes more pro-inflammatory cytokine producing, It seems UA is a risk factor to central nervous system disease. As Alvarez-Lario said (Alvarez, Macarrón, 2011), if UA was a waste or harmful product, it poorly explained why our kidneys recover 90% of filtered UA, instead of eliminating it. UA as a natural antioxidant plays an important role on induction of inflammatory response and on anti-oxidative stress in peripheral and central tissue (Glantzounis et al, 2005). In cerebral system, UA have displayed protective effects on neurons, and might been correlated

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