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Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas.

Abstract

The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound.

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  • Authors

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    Source

    Biomaterials 29:24-25 pg 3451-60

    MeSH

    Alanine Transaminase
    Animals
    Antioxidants
    Aspartate Aminotransferases
    Catalase
    Cell Line, Tumor
    Doxorubicin
    Female
    Flow Cytometry
    Fullerenes
    Glutathione
    Glutathione Peroxidase
    Glutathione Reductase
    Humans
    Hydroxybutyrate Dehydrogenase
    L-Lactate Dehydrogenase
    Liver
    Malondialdehyde
    Mammary Neoplasms, Animal
    Microscopy, Fluorescence
    Rats
    Rats, Sprague-Dawley
    Superoxide Dismutase
    Thiobarbituric Acid Reactive Substances

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18501960

    Citation

    TY - JOUR T1 - Potential hepatoprotective effects of fullerenol C60(OH)24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. AU - Injac,Rade, AU - Perse,Martina, AU - Obermajer,Natasa, AU - Djordjevic-Milic,Vukosava, AU - Prijatelj,Matevz, AU - Djordjevic,Aleksandar, AU - Cerar,Anton, AU - Strukelj,Borut, Y1 - 2008/05/27/ PY - 2008/3/16/received PY - 2008/4/28/accepted PY - 2008/5/27/aheadofprint PY - 2008/5/27/pubmed PY - 2008/12/17/medline PY - 2008/5/27/entrez SP - 3451 EP - 60 JF - Biomaterials JO - Biomaterials VL - 29 IS - 24-25 N2 - The aim of this study was to investigate the potential protective role of fullerenol C60(OH)24 on doxorubicin-induced liver toxicity using in vivo (female Sprague-Dawley rats) and in vitro (human hepatocellular carcinoma - HepG2; colorectal adenocarcinoma cell lines - Caco-2) approaches. The first (healthy control) and second (control with chemically induced mammary carcinomas) group received saline only. The third, fourth and fifth group (all with breast cancer) were injected (i.p.) with a single dose of doxorubicin (8mg/kg), doxorubicin/fullerenol (100mg/kg of fullerenol 30min before administration of 8mg/kg doxorubicin) and fullerenol (100mg/kg), respectively. Two days after treatment, the rats were sacrificed. Results showed that treatment with doxorubicin alone caused significant changes in the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), as well as in the levels of malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), total antioxidant status (TAS), glutathione reductase (GR), catalase (CAT) and superoxide dismutase (SOD) in the liver tissue. These effects were significantly reduced for all investigated parameters by pre-treatment with fullerenol but not for the MDA and GSH level. The HepG2 and Caco-2 cell lines were continuously treated with fullerenol for 12h, 24h, 48h and 96h at concentrations of 10microg/mL and 44microg/mL. With the aim of evaluating the modulating activity of fullerenol on doxorubicin-induced hepatotoxicity, the cell lines were simultaneously treated with doxorubicin (1microm; 5microm) and fullerenol (10microg/mL; 44microg/mL) in different combinations. When the cells are treated with 5microm doxorubicin along with the fullerenol, we can see a significant improvement of the cell capability during the entire time-line. We can conclude that fullerenol has cytotoxic effects on HepG2 by itself, but when the oxidative stress is too high the cytotoxic effects of fullerenol are overcome by its protective role as a strong antioxidant compound. SN - 0142-9612 UR - https://www.unboundmedicine.com/medline/citation/18501960/Potential_hepatoprotective_effects_of_fullerenol_C60_OH_24_in_doxorubicin_induced_hepatotoxicity_in_rats_with_mammary_carcinomas_ L2 - http://linkinghub.elsevier.com/retrieve/pii/S0142-9612(08)00325-6 ER -