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 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-alpha mRNA expression in liver tissue, which resulted in prevention of liver damage induced by Con A in mice.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Mei
M
Gao
Jianjun
J
Zhang
Gengtao
G
Liu
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D003208:Concanavalin A / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004149:Dioxoles / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal; D015870:Gene Expression / Q000187:drug effects; D006520:Hepatitis, Animal / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020011:Protective Agents / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000276:Adjuvants, Immunologic; D004149:Dioxoles; D004365:Drugs, Chinese Herbal; D020011:Protective Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; C041398:7,7'-dimethoxy-(4,4'-bi-1,3-benzodioxole)-5,5'-dicarboxylic acid dimethyl ester