Uric Acid Induces Inflammation, Hepatocyte Apoptosis and Deterioration of Liver Function

ABSTRACT

@#Introduction: Uric acid is a common cause of liver tissue damage due to its hepatotoxic effect. This study is aimed to investigate (1) the effect of uric acid on liver damage which can be seen from the serum levels of SGOT and SGPT, (2) the inflammatory response demonstrated by TLR-4 and MCP-1 mRNA expression, and (3) the proportion of hepatocytes apoptosis in mice. Methods: A total of 25 adult male Swiss-Webster mice were divided into five groups one control group and four uric acid groups (AU7, AU14, AU21 and AU28). The uric acid groups were administered with 125 mg/kgBW uric acid for 7, 14, 21, and 28 days. Following the treatment, mice were terminated and the liver was harvested. Blood sample was taken from retro-orbital vein to assess serum uric acid, SGOT, and SGPT levels. RT-PCR was performed to examine the mRNA expressions of TLR-4 and MCP-1. TUNEL staining was used to assess the proportion of apoptotic hepatocytes. Results: Induction of uric acid caused hyperuricemia, increased expression of TLR-4 and MCP-1 mRNA significantly (p<0.05) which indicated an inflammatory reaction. The levels of SGOT and SGPT were elevated significantly (p<0.05), as well as the number of hepatocyte apoptosis (p<0.05). Conclusion: Hyperuricemia affected the inflammatory response by increasing the mRNA expression of TLR-4 and MCP-1. An increased number of apoptotic hepatocytes was likely caused by the ongoing inflammatory reaction during the induction of uric acid.