Dose- and Time-Dependent Effects of Luteolin on Liver Metallothioneins and Metals in Carbon Tetrachloride-Induced Hepatotoxicity in Mice

被引:23
作者
Domitrovic, Robert [1 ]
Jakovac, Hrvoje [2 ]
Grebic, Damir [2 ]
Milin, Cedomila [1 ]
Radosevic-Stasic, Biserka [2 ]
机构
[1] Univ Rijeka, Sch Med, Fac Med, Dept Chem & Biochem, Rijeka 51000, Croatia
[2] Univ Rijeka, Fac Med, Dept Physiol & Immunol, Rijeka 51000, Croatia
关键词
Carbon tetrachloride; Hepatotoxicity; Luteolin; Metallothionein; Trace elements and minerals; Mice;
D O I
10.1007/s12011-008-8181-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The aim of this study was to investigate the protective effect of luteolin on liver Ca, Mg, Zn, Cu, Fe, and Mn content in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. Additionally, liver metallothionein (MT) expression was studied. Luteolin was administered intraperitoneally (i.p.) as a single 5- or 50-mg/kg dose or once daily for two consecutive days, respectively. Two hours after the last injection, the mice were treated with CCl4 (20 mg/kg, i.p.). CCl4 injection reduced hepatic level of all metals except Ca, with an intense cytoplasmic staining pattern in hepatocytes located in periportal areas, indicating induction of MTs. Pretreatment with 50 mg/kg of luteolin for 2 days remarkably elevated metal content to control values (Mg and Cu) or even above them (Zn and Fe). Luteolin pretreatment increased pericentral MTs immunopositivity and histological architecture improvement in a time- and dose-dependent manner, being the most prominent in mice pretreated with 50 mg/kg for 2 days. The liver in this group showed pronounced MT expression in almost all hepatocytes throughout the liver parenchyma. In conclusion, these results suggest the protective effect of luteolin on CCl4-induced hepatotoxicity and an enhancement of hepatocyte proliferative capabilities.
引用
收藏
页码:176 / 185
页数:10
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