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Dose- and time-dependent effects of luteolin on liver metallothioneins and metals in carbon tetrachloride-induced hepatotoxicity in mice

The aim of this study was to investigate the protective effect of luteolin on liver trace element and mineral content in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. Additionally, liver metallothionein (MT) expression was studied immunohistologically. Luteolin was administered intraperitoneally (i.p.) as a single 5 or 50 mg/kg dose, or once daily for 2 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 MT. Pretreatment with 50 mg/kg of luteolin for 2 d remarkably elevated metal content to control values (Mg and Cu) and even above them (Zn and Fe). Luteolin pretreatment increased pericentral MT 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 d. 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.

carbon tetrachloride; hepatotoxicity; luteolin; mettalothionein; trace elements and minerals; mice

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