Upregulation of Sirt1 in carbon-tetrachloride–induced acute liver injury

Sirtuin 1 (Sirt1) has been the focus of intense scrutiny because of its longevity activity. Recent studies also revealed the important role of Sirt1 in metabolic liver diseases. The present study was designed to elucidate the pathophysiological significance of Sirt1 in CCl(4)-induced acute liver injury (ALI). The expression of Sirt1 in liver tissue of mice with CCl(4)-induced ALI was determined by real-time polymerase chain reaction and western blotting. Sirt1 inhibitor nicotinamide (NAM) was administrated to investigate the role of Sirt1 in hepatocyte damage, leukocyte infiltration, and proinflammatory cytokine production. Results indicated that the messenger RNA and protein level of Sirt1 in the liver was gradually increased after CCl(4) administration. Inhibition of Sirt1 by its inhibitor (NAM) exacerbated liver injury, as evidenced by increased serum aminotransferases (alanine aminotransferase and aspartate aminotransferase) levels and more-severe histological damage. The worst liver injury was accompanied by higher myeloperoxidase acitivity in liver tissue and increased circulating levels of both tumor necrosis factor alpha and interleukin-6. These data indicated that the induction of Sirt1 might provide protective effects during CCl(4)-induced ALI. These findings suggest that Sirt1 might be an endogenous hepatoprotective target with potential pharmacological value in inflammation-based liver diseases.