Tangeritin attenuates oxidative stress, apoptosis and inflammation in cadmium-induced cardiotoxicity in rats by activating Nrf2 signaling pathway

Abstract

Purpose: To determine the effect of tangeritin on cadmium-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced by intra-gastric administration of 5 mg/kg cadmium chloride to rats, once daily for 4 weeks. The animals were treated with tangeritin at 10 and 20 mg/kg p.o. 60 min before the administration of cadmium, for 4 weeks. Thereafter, the concentrations of cadmium in serum and cardiac tissue were determined, and markers of cardiac function, antioxidant enzyme activities and levels of pro-inflammatory mediators were evaluated in cardiac tissues. Histopathological examination and western blot assay were also performed. Results: Treatment with tangeritin significantly decreased the cadmium levels in the heart tissue and serum of the cadmium-exposed rats, when compared to the negative control group (p < 0.01). There was significant decrease in cardiac function markers in the tangeritin-treated rats, relative to negative control group (p < 0.01). However, antioxidant enzyme activity and levels of pro-inflammatory mediators were attenuated in the cardiac tissues of cadmium-treated rats by tangeritin treatment. Expressions of HO-1 and Nrf-2 were significantly enhanced in the cardiac tissues of tangeritin-treated group, relative to negative control group (p < 0.01). Histopathology revealed that tangeritin attenuated cadmium-induced cardiac injury in cadmium-exposed rats. Conclusion: These results demonstrate the protective effect of tangeritin against cadmium-induced cardiotoxicity via attenuation of oxidative stress and pro-inflammatory mediators.