Effect of diphenyl dimethyl bicarboxylate on concanavalin A-induced liver injury in mice

Diphenyl dimethyl bicarboxylate (DDB) is a hepatoprotectant and used in the treatment of chronic viral hepatitis patients in China. The aim of the present paper was to investigate the effect of DDB on liver injury mediated by immune response in concanavalin A (Con A)-treated mice. A dose of Con A 30 mg/kg was injected via the tailvein to induce liver injury in mice. Serum alanine transaminase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL) and tumor necrosis factor alpha (TNF-alpha) level as well as liver TNF-alpha mRNA expression were determined. The following results were obtained: (1) Prior oral administration of DDB 150 mg/kg markedly reduced the elevated serum ALT, TBA and TBIL levels, and the liver lesions in Con A-treated mice; (2) DDB significantly inhibited the elevation of serum TNF-alpha and liver TNF-alpha mRNA expression 2 h after Con A injection; (3) DDB significantly inhibited hepatocyte nuclear DNA fragmentation 12 h after Con A injection; (4) DDB dose-dependently prevented the direct DNA damage induced by CuSO4-Phen-Vit C-H2O2 system in vitro, and the ex vivo experiment also showed that the administration of DDB reduced the susceptibility of mouse liver nuclei DNA to CuSO4-Phen-Vit C-H2O2 system. These results suggest that DDB could directly protect hepatocyte DNA from oxidative damage, and inhibit TNF-alpha mRNA expression in liver tissue, which resulted in prevention of liver damage induced by Con A in mice.