Methotrexate-induced hepatotoxicity in rats and the therapeutic properties of vitamin E: a histopathologic and flowcytometric research

Creative Commons License

Akman A. U., ERİŞGİN Z., Turedi S., TEKELİOĞLU Y.

CLINICAL AND EXPERIMENTAL HEPATOLOGY, vol.9, no.4, pp.359-367, 2023 (ESCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 9 Issue: 4
  • Publication Date: 2023
  • Doi Number: 10.5114/ceh.2023.132251
  • Journal Indexes: Emerging Sources Citation Index (ESCI), Scopus
  • Page Numbers: pp.359-367
  • Karadeniz Technical University Affiliated: Yes


Aim of the study: Methotrexate (MTX) causes oxidative stress-related liver damage. Our objective was to investigate the protective effects of vitamin E against MTX-induced hepatotoxicity through histopathological methods and flow cytometry. Material and methods: The rats were assigned to four groups: Control (2 ml saline for 5 days), MTX (20 mg/kg intraperitoneally (i.p.) only on the initial day of the study), MTX + vitamin E (20 mg/kg MTX (i.p.) only on the first day, and 100 mg/kg vitamin E (i.p.) was applied for 5 days during the study), Vitamin E (100 mg/kg of vitamin E (i.p.) was given for five days). Histopathologic changes and the flow cytometric apoptotic index were evaluated for liver tissue. The Kruskal-Wallis test was used for comparisons between groups. The statistical significance level was accepted asp < 0.05.Results: In the histopathological analysis, hepatocyte degeneration, dilatation of sinusoids, mononuclear cell infiltration, hydropic degeneration in hepatocytes, vacuolization, and pycnotic nucleus were observed in the MTX group. In the MTX + vitamin E group, hepatocyte degeneration, pycnotic nuclei, and dilatation in sinusoids were significantly lower compared to the MTX group. In the MTX group, glycogen accumulation in hepatocytes was lower compared to the control group. In the MTX + vitamin E group, glycogen accumulation in hepatocy-tes was higher compared to the MTX group. The flowcytometric apoptotic index (AI) percentage in the MTX group was 34.4% and in the MTX + vitamin E group the value was 9.4%.Conclusions: Our results demonstrated that vitamin E ameliorates MTX-induced liver damage. Co-using vitamin E and MTX drugs will be beneficial for the treatment of various diseases.