Protective Effects of Biochanin A against Methotrexate-Induced Acute Liver Injury in Rats

Indian Journal of Pharmaceutical Education and Research

  • Erdem Kamil Ozer1Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, TURKEY.
  • Mustafa Tugrul Goktas2Department of Pharmacology, Faculty of Medicine, Yildirim Beyazit University, Ankara, TURKEY.
  • Aysun Toker3Department of Biochemistry, Faculty of Medicine, Necmettin Erbakan University, Konya, TURKEY.
  • Ceyhan Ugurluoglu4Department of Pathology, Faculty of Medicine, Selcuk University, Konya, TURKEY.
  • Hulagu Bariskaner1Department of Pharmacology, Faculty of Medicine, Selcuk University, Konya, TURKEY.

Volume 51 Issue 4s Pages s741-s746

DOI: 10.5530/ijper.51.4s.107

Abstract

Background: Methotrexate (MTX) is one of the most commonly used chemotherapeutic agents in the treatment of cancer patients, however its therapeutic use is limited due to dose dependent hepatotoxicity caused by oxidative damage. Biochanin A (BCA), a naturally occurring dietary isoflavone, has strong cytoprotective, anti-inflammatory, and antioxidant properties. Although protective actions of BCA against various chemicalinduced hepatotoxicity including that of carbon tetrachloride and arsenic, none of the studies was made on MTX-induced acute liver injury.Methods: Wistar rats were separated into four groups; Control, MTX, Control+BCA, MTX+BCA. BCA (50 mg/kg/day) or vehicle (dimethyl sulfoxide; 1 mL/kg/day) with the same volume was intraperitoneally injected for 5 days. At sixth day, a single dose of MTX (20 mg/kg) was injected to rats. Twenty-four h after the MTX administration, rats were sacrificed and then blood and liver samples were obtained for biochemical and histopathologic analyses.Results: MTX increased the serum AST, ALT, and LDH levels. Furthermore, malondialdehyde (an indicator of oxidative injury) and myeloperoxidase (an indicator of neutrophil infiltration) levels increased, while total glutathione levels (an indicator of antioxidant status) decreased in liver. MTX-induced hepatotoxicity was also observed histopathologically. BCA substantially improved these alterations induced by MTX administration.Conclusion: These results indicate that BCA may be useful in preventing the MTX-induced acute liver injury due to its antioxidant and anti-inflammatory properties.

Keywords

  • Methotrexate
  • Hepatotoxicity
  • Biochanin A
  • Protective effects
IJOPP

Loading…