Melatonin ameliorates arsenic-induced cardiotoxicity through the regulation of the Sirt1/Nrf2 pathway in rats

Fatemeh Yarmohammadi, Samira Barangi, Seyed Hamid Aghaee-Bakhtiari, Hossein Hosseinzadeh, Zahra Moosavi, Russel J. Reiter, A. Wallace Hayes, Soghra Mehri, Gholamreza Karimi

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre-treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As-mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down-regulated autophagy markers such as Beclin-1 expression and the LC3-II/I ratio. Moreover, the cardiac expression of cleaved-caspase-3 and Bax/Bcl-2 ratio was decreased by Mel pretreatment. Reduced expression of miR-34a and miR-144 by As were reversed by Mel. The histopathological changes of cardiac injury associated with As exposure was moderated by Mel. Mel may improve As-induced cardiac dysfunction through anti-oxidative, anti-apoptotic, and anti-autophagic mechanisms.

Original languageEnglish (US)
Pages (from-to)620-635
Number of pages16
JournalBioFactors
Volume49
Issue number3
DOIs
StatePublished - May 1 2023
Externally publishedYes

Keywords

  • MicroRNA-144
  • MicroRNA-34a
  • apoptosis
  • autophagy
  • oxidative stress

ASJC Scopus subject areas

  • Molecular Medicine
  • Biochemistry
  • Clinical Biochemistry

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