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

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.