Molecular and Cellular Biochemistry

, Volume 385, Issue 1–2, pp 215–223 | Cite as

Beneficial effects of Chrysin against Methotrexate-induced hepatotoxicity via attenuation of oxidative stress and apoptosis

  • Nemat Ali
  • Summya Rashid
  • Sana Nafees
  • Syed Kazim Hasan
  • Sarwat Sultana


Methotrexate (MTX), a folic acid antagonist, an effective chemotherapeutic agent is used in the treatment of a wide range of tumors and autoimmune diseases. Moreover, hepatotoxicity limits its clinical use. Several studies have already confirmed that the oxidative stress plays a major role in the pathogenesis of MTX-induced damage in the various organs especially in liver. The aim of this study was to determine the protective effect of Chrysin against MTX-induced hepatic oxidative stress and apoptosis in rats. In the present study, efficacy of Chrysin was investigated against hepatotoxicity caused by MTX in terms of biochemical investigations of antioxidant enzymes, apoptosis, and histopathological alteration in rat liver. In the MTX-treated group there was a significant increase in alanine transaminase, aspartate aminotransferase, lactate dehydrogenase activity and malondialdehyde content as well as decreased glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase activities and reduced glutathione content were also observed compared to the control group as a marker of oxidative stress. Histopathological alterations and apoptosis through the immunopositive staining of p53, cleaved caspases-3 and Bcl-2-associated X protein in rat liver were observed. Pretreatment of Chrysin at both doses prevents the hepatotoxicity by ameliorating oxidative stress, histopathological alterations, and apoptosis and thus our results suggest that Chrysin has a protective effect against hepatotoxicity induced by MTX and it may, therefore, improve the therapeutic index of MTX if co-administration is done.


Methotrexate Oxidative stress Apoptosis Hepatotoxicity Chrysin 



The author (Sarwat Sultana) is thankful to University Grants Commission (New Delhi, India), under Special Assistance Programme for Departmental Research Support-II (SAP DRS-II) and Basic Scientific Research (BSR) for providing funds to carry out this work.

Conflict of interest

The authors declare that there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Nemat Ali
    • 1
  • Summya Rashid
    • 1
  • Sana Nafees
    • 1
  • Syed Kazim Hasan
    • 1
  • Sarwat Sultana
    • 1
  1. 1.Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of ScienceJamia Hamdard (Hamdard University)Hamdard NagarIndia

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