Sodium arsenite-induced myocardial bruise in rats: Ameliorative effect of naringin via TGF-β/Smad and Nrf/HO pathways

Chem Biol Interact. 2016 Jun 25:253:66-77. doi: 10.1016/j.cbi.2016.05.015. Epub 2016 May 10.

Abstract

Background: Arsenic poisoning is a serious medical condition caused by consumption of contaminated food and water. Cardiovascular toxicity is one of the important risk factors associated with arsenic toxicity.

Aim: To elucidate efficacy and possible mechanism of action of naringin in arsenic-induced cardiac toxicity in laboratory rats.

Materials and methods: Arsenic toxicity was induced in Sprague-Dawley rats by sodium arsenite (5 mg/kg, p.o., 28 days). Rats were either concomitantly treated with vehicle (5 mL/kg, p.o.) or naringin (20, 40 and 80 mg/kg, p.o.) for 28 days. Chronic administration of sodium arsenite caused significant alterations in electrocardiographic, hemodynamic and left ventricle contractile functions.

Results: Treatment with naringin (40 and 80 mg/kg, p.o.) significantly restored (p < 0.05) these altered myocardial functions. Administration of naringin (40 and 80 mg/kg, p.o.) significantly inhibited (p < 0.05) arsenite-induced increased cardiac markers (LDH, CK-MB, AST, ALT, and ALP) and altered lipid metabolism (total cholesterol, triglyceride, LDL, HDL, and VLDL). The elevated level of heart oxido-nitrosative stress and decreased cardiac Na-K-ATPase level after arsenite administration was significantly attenuated (p < 0.05) by naringin (40 and 80 mg/kg, p.o.) treatment. Naringin also significantly increased (p < 0.05) myocardial mitochondrial enzymes (I-IV) activity. Arsenite-induced alteration in heart Nrf-2, HO-1, Smad-3, and TGF-β mRNA expression were significantly restored (p < 0.05) by naringin (40 and 80 mg/kg) treatment. Treatment with naringin (40 and 80 mg/kg) significantly inhibited (p < 0.05) arsenite-induce apoptosis revealed by flow cytometric analysis. Naringin administration reduced histopathological aberrations (measured using transmission electron microscopy) induced by sodium arsenite.

Conclusion: The results of present investigation suggest that naringin ameliorates arsenite-induced cardiotoxicity via modulation of TGF-β/Smad-3 and Nrf-2/HO-1 pathways along with a reduction in myocardial apoptosis.

Keywords: Apoptosis; Cardiotoxicity; Naringin; Sodium arsenite; Transmission electron microscopy.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Arsenites / toxicity
  • Cells, Cultured
  • Electrocardiography
  • Flavanones / pharmacology*
  • Flow Cytometry
  • Heart Injuries / etiology
  • Heart Injuries / metabolism
  • Heart Injuries / pathology
  • Heme Oxygenase (Decyclizing) / genetics
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Hemodynamics / drug effects
  • Male
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocardium / pathology
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Smad Proteins / genetics
  • Smad Proteins / metabolism*
  • Sodium Compounds / toxicity
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*
  • Ventricular Function, Left / drug effects

Substances

  • Arsenites
  • Flavanones
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • Smad Proteins
  • Sodium Compounds
  • Transforming Growth Factor beta
  • sodium arsenite
  • Heme Oxygenase (Decyclizing)
  • Sodium-Potassium-Exchanging ATPase
  • naringin