Autophagy Regulation in the Context of Arsenic Trioxide-Induced Cardiotoxicity via Flaxseed Oil: Myosin Heavy Chain, BNP and SIRT1 genetic Association

Document Type : Original Article


Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Center, El Buhouth St., Dokki, Cairo, Egypt.


Arsenic is extensively utilized to cure patients with acute leukemia nevertheless; its application has been limited due to its cardiotoxicity. Additionally, arsenic damaged mitochondria manifested via limiting mitochondrial membrane potential, diminishing cytochrome c level and production of mitochondrial reactive oxygen species (ROS). Furthermore, silent information regulator of transcription (SIRT1) as an autophagy biomarker was widely implicated in numerous indispensable pathways of cardiovascular diseases. Therefore, the aim of the present study was designed to investigate the cardioprotective effect and the underlying mechanism of flaxseed oil (FLX), vitamin C and their combination versus arsenic trioxide toxicity via crosslinking myosin heavy chain (α-MHC, β-MHC), brain natriuretic peptide (BNP) and autophagy biomarker SIRT1signaling pathway.

Male Wistar albino rats were administrated arsenic trioxide (3 mg/kg) for one month. Consequently animals were co-treated via FLX (1ml/kg), vitamin C. (200 mg/kg) in addition to their combination for one month. Further, Aspartate Aminotransferase (AST), C- reactive protein (CRP) and malondialdehyde (MDA) biochemical analyses were assessed. Molecular analysis for α-MHC, β-MHC, BNP and SIRT1 gene expression were also investigated.

Arsenic myocardial injury recorded a significant increment in AST, CRP as well as MDA levels that were further modulated upon co-treatment. RT-PCR Results declared a significant reduction in both α-MHC and SIRT1gene expression upon arsenic toxicity. Nevertheless, a significant up-regulation appeared in co-treated groups. On the other hand, a significant elevation in both β-MHC and BNP was reported. Meanwhile, a significant down regulation was observed post the co-treatment. In conclusion, FLX could be a promising therapeutic regimen against myocardial injury. In addition, its prospective role could be enhanced by combination with V.C.


Main Subjects

Volume 65, Issue 131 - Serial Number 13
Special Issue: Chemistry and Global Challenges (Part A)
December 2022
Pages 1137-1146
  • Receive Date: 01 August 2022
  • Revise Date: 10 September 2022
  • Accept Date: 15 September 2022