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

• Na-arsenite caused alterations in ECG, hemodynamic and LV-contractile functions.
• Naringin restored these altered myocardial functions.
• Naringin increased myocardial mitochondrial enzymes (I-IV) activity.
• Myocardial Nrf-2, HO-1, Smad-3 and TGF-β mRNA expression were restored by naringin.
• Naringin inhibited arsenite-induced apoptosis and ultramicroscopical aberrations.

BackgroundArsenic 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.AimTo elucidate efficacy and possible mechanism of action of naringin in arsenic-induced cardiac toxicity in laboratory rats.Materials and methodsArsenic 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.ResultsTreatment 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.ConclusionThe 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.

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