Attenuation of arsenic trioxide induced cardiotoxicity through flaxseed oil in experimental rats

Redox Rep. 2017 Nov;22(6):346-352. doi: 10.1080/13510002.2017.1289313. Epub 2017 Feb 17.

Abstract

Objectives: Arsenic trioxide (As2O3) is a potent drug for acute promyelocytic leukaemia, but its clinical trials are allied with some serious adverse events mainly cardiac functional abnormalities. So the objective of our investigation is to identify the cardioprotective action of flaxseed oil (FSO), a natural compound against As2O3 induced cardiotoxicity.

Methods: Male wistar rats were treated with As2O3 (4 mg/kg) to induce cardiotoxicity. FSO (250 and 500 mg/kg) was given in combination with As2O3 for evaluating its cardioprotective efficacy.

Results: Treatment with As2O3 resulted in deposition of arsenic in heart tissue, increased cardiac marker enzymes release, lipid peroxidation (LPO), oxidative insults and pathological damages in the heart. Co-treatment with FSO (500 mg/kg) significantly reduced the arsenic accumulation, cardiac marker enzymes, LPO and cardiac structural alterations. FSO treatment significantly improved cardiac glutathione content, antioxidant enzymes and reduced the pathological damages in cardiac tissue. Gas chromatographic-mass spectrometry analysis revealed that the major fatty acid content in the FSO is alpha-linolenic acid, which has a strong milieu in cardiac health.

Conclusion: The results of the current investigation suggested that FSO is an effective agent in reducing arsenic-induced cardiac toxicity and can be used as an adjunct/dietary supplement for the cancer patients on As2O3 therapy.

Keywords: Arsenic trioxide; alpha-linolenic acid; flax seed oil; lipid peroxidation; omega-3 fatty acid; oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Arsenic Trioxide
  • Arsenicals
  • Cardiotoxicity / drug therapy*
  • Cardiotoxicity / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Linseed Oil / therapeutic use*
  • Lipid Peroxidation / drug effects
  • Male
  • Oxidative Stress / drug effects
  • Oxides / toxicity*
  • Rats
  • Rats, Wistar

Substances

  • Antioxidants
  • Arsenicals
  • Oxides
  • Linseed Oil
  • Arsenic Trioxide

Grants and funding

We are thankful to the University Grants Commission, New Delhi for awarding the BSR-Meritorious Fellowship to Dr MVV (No. F.4-1/2006 (BSR)/11-29/2008(BSR)).