肝损伤
刀豆蛋白A
肝细胞
化学
肿瘤坏死因子α
丙氨酸转氨酶
体内
内科学
天冬氨酸转氨酶
DNA断裂
内分泌学
分子生物学
药理学
体外
生物
医学
生物化学
细胞凋亡
程序性细胞死亡
酶
碱性磷酸酶
生物技术
作者
Mei Gao,Jianjun Zhang,Geng-Tao Liu
标识
DOI:10.1111/j.1478-3231.2005.01140.x
摘要
Abstract: 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 α (TNF‐α) level as well as liver TNF‐α 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‐α and liver TNF‐α 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 CuSO 4 –Phen–Vit C–H 2 O 2 system in vitro , and the ex vivo experiment also showed that the administration of DDB reduced the susceptibility of mouse liver nuclei DNA to CuSO 4 –Phen—Vit C–H 2 O 2 system. These results suggest that DDB could directly protect hepatocyte DNA from oxidative damage, and inhibit TNF‐α mRNA expression in liver tissue, which resulted in prevention of liver damage induced by Con A in mice.
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