The effects of casticin and myricetin on liver damage induced by methotrexate in rats

Objective(s): In this study, we evaluated the therapeutic effects of casticin and myricetin on liver  damage induced by methotrexate in rats.Materials and Methods: Thirty-six male rats were used for the study and divided into 6 groups: control, methotrexate, casticin, myricetin, casticin+methotrexate, and myricetin+methotrexate. It was performed by methotrexate (20 mg/kg single dose, IP) in methotrexate, casticin+methotrexate and myricetin+methotrexate groups. Casticin 200 mg/kg dose was given to casticin and casticin+methotrexate groups. Myricetin 50 mg/kg dose was given to myricetin and myriceytin+methotrexate groups. At the end of the experiment, liver tissues were removed for the purpose of histopathological, biochemical and immunohistochemical assessments. Results: In our study, we have detected that MDA levels increased and activities of antioxidant enzymes SOD, CAT, and GPX decreased in the methotrexate group compared to the other groups, but the level of MDA decreased and activities of these enzymes increased in casticin+methotrexate and myricetin+methotrexate groups compared to the methotrexate group. In immunohistochemical examinations of control, casticin and myricetin groups in liver tissues no caspase-3 and 8-OHdG expressions were observed. In the MTX group, caspase-3 and 8-OHdG expressions were seen at the severe levels. Caspase-3 and 8-OHdG expressions were mild in hepatocytes in the casticin+methotrexate and myricetin+methotrexate groups. When the liver tissues of the rats in the methotrexate group were examined, severe pathological damage was detected both in the parietal region and in the portal region.Conclusion: By looking at these results, we can say that casticin and myricetin are effective against liver damage induced by methotrexate.