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

作者：Domitrovic Robert^*; Jakovac Hrvoje; Grebic Damir; Milin Cedomila; Radosevic Stasic Biserka

来源：Biological Trace Element Research, 2008, 126(1-3): 176-185.

DOI：10.1007/s12011-008-8181-0

• Carbon tetrachloride
• Hepatotoxicity
• Luteolin
• Metallothionein
• Trace elements and minerals
• Mice

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 (CCl(4))-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 CCl(4) (20 mg/kg, i.p.). CCl(4) 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 CCl(4)-induced hepatotoxicity and an enhancement of hepatocyte proliferative capabilities.

• 出版日期2008-12