Liver protection by bis(maltolato)zinc(II) complex.
The aim of this study was to perform screening of a novel drug for treating liver injury. Bis(maltolato)zinc(II) complex [Zn(Mal)(2)], which was previously reported to possess insulinomimetic activity, was found to have potency against experimentally induced liver injury both in vitro and in vivo. Cultured rat hepatocytes were treated with bromobenzene for 24 h to induce cellular injury. Zn(Mal)(2) of various concentrations was added along with bromobenzene in order to evaluate the hepatoprotective activity of Zn(Mal)(2) in vitro. The number of viable hepatocytes decreased by 42% in the culture with bromobenzene. However, hepatocyte viability was maintained when Zn(Mal)(2) was added to the bromobenzene culture. The hepatoprotective activity of Zn(Mal)(2) in vivo was investigated using a concanavalin A-induced liver injury model in BALB/c mice. Changes in serum aminotransferase activities and the secretion of several cytokines were measured. The hepatoprotective effect of Zn(Mal)(2) was also demonstrated in vivo by the suppression of serum aspartate aminotransferase and alanine aminotransferase elevation. No significant changes in serum cytokines associated with the induction of hepatic damage were observed in the concanavalin A-induced injury model. However, examination of concanavalin A-treated mouse splenocytes revealed a dose-dependent suppression of cytokine secretions by Zn(Mal)(2). Zn(Mal)(2) possessed hepatoprotective activity and might exert its effect by a number of mechanisms.
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
Masaya
M
Kawase
Noritaka
N
Kagaya
Soh-Ichiro
S
Akamatsu
Akiko
A
Kamiyoshi
Shin-Ichi
S
Muto
Yoh-Ichi
Y
Tagawa
Kiyohito
K
Yagi
D000818:Animals; D001969:Bromobenzenes; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury; D003208:Concanavalin A; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D008107:Liver Diseases / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D000637:Transaminases / Q000097:blood
D001969:Bromobenzenes; D016207:Cytokines; D009942:Organometallic Compounds; C424132:bis(maltolato)zinc(II); D003208:Concanavalin A; C032036:bromobenzene; D000637:Transaminases