title: Sodium arsenite-induced myocardial bruise in rats: Ameliorative effect of naringin via TGF-β/Smad and Nrf/HO pathways.
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.
  
  
  OBJECTIVE
  To elucidate efficacy and possible mechanism of action of naringin in arsenic-induced cardiac toxicity in laboratory rats.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, 411038, India.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Adil
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, 411038, India.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Kandhare
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, 411038, India.
authors.forename: Pinaki
authors.initials: P
authors.lastname: Ghosh
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, 411038, India. Electronic address: drsbodh@gmail.com.
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018053:Arsenites / Q000633:toxicity; D002478:Cells, Cultured; D004562:Electrocardiography; D044950:Flavanones / Q000494:pharmacology*; D005434:Flow Cytometry; D006335:Heart Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism*; D017670:Sodium Compounds / Q000633:toxicity; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D018053:Arsenites; D044950:Flavanones; D051267:NF-E2-Related Factor 2; D017382:Reactive Oxygen Species; D051785:Smad Proteins; D017670:Sodium Compounds; D016212:Transforming Growth Factor beta; C017947:sodium arsenite; D006419:Heme Oxygenase (Decyclizing); D000254:Sodium-Potassium-Exchanging ATPase; C005274:naringin
keywords: Apoptosis; Cardiotoxicity; Naringin; Sodium arsenite; Transmission electron microscopy