title: Dose- and time-dependent effects of luteolin on liver metallothioneins and metals in carbon tetrachloride-induced hepatotoxicity in mice.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, School of Medicine, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. robertd@medri.hr
authors.forename: Robert
authors.initials: R
authors.lastname: Domitrović
authors.forename: Hrvoje
authors.initials: H
authors.lastname: Jakovac
authors.forename: Damir
authors.initials: D
authors.lastname: Grebić
authors.forename: Cedomila
authors.initials: C
authors.lastname: Milin
authors.forename: Biserka
authors.initials: B
authors.lastname: Radosević-Stasić
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D003300:Copper / Q000378:metabolism; D007150:Immunohistochemistry; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D008668:Metallothionein / Q000378:metabolism*; D008670:Metals / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015032:Zinc / Q000378:metabolism
chemical_list: D008670:Metals; D008345:Manganese; D003300:Copper; D008668:Metallothionein; D007501:Iron; D008274:Magnesium; D015032:Zinc; D047311:Luteolin