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

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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.

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Acknowledgments

This research was supported by grants from Ministry of Science, Education and Sport, Republic of Croatia (projects No. 062-0000000-3554 and 062-0621341-0061).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, School of Medicine, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000, Rijeka, Croatia

    Robert Domitrović & Čedomila Milin

  2. Department of Physiology and Immunology, Medical Faculty, University of Rijeka, 51000, Rijeka, Croatia

    Hrvoje Jakovac, Damir Grebić & Biserka Radošević-Stašić

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  1. Robert Domitrović
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  2. Hrvoje Jakovac
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  3. Damir Grebić
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  4. Čedomila Milin
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  5. Biserka Radošević-Stašić
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Correspondence to Robert Domitrović.

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Domitrović, R., Jakovac, H., Grebić, D. et al. Dose- and Time-Dependent Effects of Luteolin on Liver Metallothioneins and Metals in Carbon Tetrachloride-Induced Hepatotoxicity in Mice. Biol Trace Elem Res 126, 176–185 (2008). https://doi.org/10.1007/s12011-008-8181-0

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  • DOI: https://doi.org/10.1007/s12011-008-8181-0

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