Evaluation of the hepatoprotective effect of different doses of curcumin and vitamin c in methotrexate-induced hepatotoxicity in mice

Background: Methotrexate, the antineoplastic and immunosuppressive drug, is used in the treatment of different types of cancers and the management of chronic inflammatory diseases. Hepatotoxicity is one of its major side effects. Objectives: The present study assesses the hepatoprotective effect of different doses of curcumin and Vitamin C in methotrexate-induced hepatotoxicity. Materials and Methods: The prospective experimental study was conducted at the College of Medicine, Mustansiriyah University, Baghdad, Iraq, and in the animal's house of the Iraqi Center for Cancer Research, Baghdad-Iraq, from November 2020 to June 2021, and comprised Swiss albino female mice aged 3–4 months and weighing 30–40 g each. The mice were divided into 6 groups, the first group was considered as control which received only distilled water, the second group was considered as methotrexate group, third and fourth groups orally supplemented with 10 mg/kg and 20 mg/kg curcumin, respectively, fifth and sixth groups orally supplemented with 100 mg/kg and 200 mg/kg Vitamin C, respectively, The experiment continued for 10 days, and on the 10th day all groups, except the control one, received 20 mg/kg methotrexate intraperitoneally to induce hepatotoxicity. Parameters measured were serum alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), and liver tissue malondialdehyde (MDA), superoxide dismutase, and glutathione. SPSS 16 was used for data analysis. Results: The results show significant hepatoprotection produced by curcumin reflected by a decrease in LDH and MDA. Vitamin C also produced a significant hepatoprotection demonstrated by a decrease in ALT, ALP, LDH, and MDA. Conclusion: Curcumin and Vitamin C were found to provide hepatoprotection against methotrexate-induced hepatotoxicity through the modulation of oxidative stress biomarkers in a dose-dependent manner.