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

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.

Figure 1.

GC–MS profiling of flax seed oil: fatty acid distribution peaks, n = 3.

Figure 2.

Effect of FSO on arsenic deposition in heart: data represented as mean ± SD, n = 6. ^aP < 0.05 vs. normal control, ^bP < 0.05 vs. As₂O₃ (4 mg/kg b.wt).

Figure 3.

Effect of FSO and As₂O₃ on serum cholesterol and triglyceride: data represented as mean ± SD, n = 6.

Figure 4.

Histopathology of heart tissue: histopathological changes occurred in rat heart tissues after As₂O₃ administration and its amelioration with FSO treatment (Hematoxylin and Eosin, 100×). (a) – normal control; (b) – FSO (500 mg/kg b.wt); (c) – As₂O₃ (4 mg/kg b.wt); (d) – As₂O₃ (4 mg/kg b.wt) + FSO (250 mg/kg b.wt), (e) – As₂O₃ (4 mg/kg b.wt) + FSO (500 mg/kg b.wt). fs – fibre separations, io – interstitial oedema, cc – capillary congestion, mh – micro-haemorrhages, ms – mild swelling.