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Protective effects of taxifolin on pazopanib-induced liver toxicity: an experimental rat model

Baran Akagunduz1, Muhammet Ozer2, Fatih Ozcıcek3

  • 1Department of Medical Oncology, Erzincan Binali Yildirim University, Fatih Street #124, 24030, Erzincan, Turkey.

Experimental Animals
|November 26, 2020
PubMed

Insights

Taxifolin effectively prevents liver damage caused by pazopanib, a cancer drug. This study shows taxifolin reduces markers of liver toxicity and improves tissue health in rats treated with pazopanib.

Area of Science:

  • Pharmacology
  • Toxicology
  • Hepatology

Background:

  • Pazopanib, a tyrosine kinase inhibitor, treats renal cell cancer and soft tissue sarcoma.
  • Pazopanib is known to cause varying degrees of hepatotoxicity.
  • Investigating protective agents against drug-induced liver injury is crucial.

Purpose of the Study:

  • To evaluate the protective effect of taxifolin against pazopanib-induced liver toxicity in a rat model.
  • To assess biochemical and histological changes in the liver following pazopanib administration.
  • To determine if taxifolin can mitigate pazopanib-induced hepatotoxicity.

Main Methods:

  • Adult rats were divided into three groups: control, pazopanib (PP), and pazopanib plus taxifolin (TPP).
  • Rats received daily oral administration of taxifolin (50 mg/kg) or vehicle for four weeks, followed by pazopanib (200 mg/kg) or vehicle.
  • Liver tissues were analyzed for malondialdehyde (MDA), glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), AST, ALT, and LDH levels. Histopathological examination was performed.

Main Results:

  • Pazopanib administration significantly increased MDA and TOS levels, while decreasing tGSH and TAS levels.
  • Hepatotoxicity markers AST, ALT, and LDH were significantly elevated in the pazopanib group.
  • Histopathological analysis revealed liver tissue damage including hemorrhage, hydropic degeneration, and necrosis in the PP group.
  • Taxifolin administration significantly improved these degenerative changes and normalized biochemical markers.

Conclusions:

  • Pazopanib induces significant oxidative stress and hepatotoxicity in rats.
  • Taxifolin demonstrates a significant protective effect against pazopanib-induced liver injury.
  • Taxifolin is a promising agent for preventing or mitigating pazopanib-induced hepatotoxicity.
Keywords:
experimental modelsliver toxicityoxidative stresspazopanibtaxifolin

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