Reduction of Serum Uric Acid Associated with Attenuation of Renal Injury, Inflammation and Macrophages M1/M2 Ratio in Hyperuricemic Mice Model.

ABSTRACT

BACKGROUND: Hyperuricemia contributed to endothelial dysfunction, activation of the RAS system, increased oxidative stress and maladaptive immune system response. M1 and M2 macrophages were known to contribute to the onset of renal fibrosis. This study aimed to look at the effect of lowering serum uric acid levels on renal injury in mice. METHODS: This study used 25 male mice, 3 months old, that divided into 5 groups. We injected uric acid intraperitoneally, 125mg/kg/day for 7 days (UA7) and 14 days (UA14), to induce hyperuricemia and then gave allopurinol 50mg/kg/day for 7 days to lower serum uric acid levels (UA7AL7 and UA14AL7). At the end of the treatment, we measured serum uric acid levels, Glomerular Injury Score (GIS) and Arteriolar Injury Score (AIS) with PAS staining, eNOS and MCP-1 expression with Reverse Transcriptase-PCR (RT-PCR), macrophages M1/M2 ratio with anti-CD68 and anti-arginase I immunohistochemical staining. Data were analyzed by one-way ANOVA and Kruskal-Wallis test. RESULTS: Uric acid injection increased serum uric acid levels in UA7 and UA14 group (p<0.05), followed by the increase in GIS and AIS. RT-PCR showed increased expression of MCP-1 and decreased expression of eNOS. M1 macrophages count was higher than control in UA7 and UA14 whereas M2 macrophages did not show any increased count, so the ratio of macrophages M1 / M2 is higher. Decrease in serum uric acid levels reduced GIS, AIS, MCP-1 expression and macrophages M1/M2 ratio (p<0.05). CONCLUSION: Reduction of serum uric acid levels significantly reduced renal injury that occurred in mice model of hyperuricemia.