Comparison of antagonistic effects of nanoparticle-selenium, selenium-enriched yeast and sodium selenite against cadmium-induced cardiotoxicity via AHR/CAR/PXR/Nrf2 pathways activation.

Selenium (Se), a nutritionally essential mineral for humans and animals, has a significant antagonistic effect on heavy metal cadmium (Cd) biotoxicity. Still, the impact of different Se sources on alleviating Cd toxicity has received only limited attention. Therefore, the purpose of the current study was to assess the mitigation level of Cd-induced cardiotoxicity by different sources such as nanoparticles of Se, Se-rich yeast, and sodium selenite (SS). The results evidenced that the presence of Cd led to a significant increase in biochemical parameters such as lactate dehydrogenase and creatine kinase, as well as histopathological lesions in the heart of chickens. Cd exposure also resulted in more extensive effects on phase I metabolism enzymes and transcript cytochrome P450 isoforms, elevated the levels of malondialdehyde (MDA), glutathione (GSH), and hydrogen peroxide (HO) and depressed total superoxide dismutase (T-SOD), copper-zinc SOD (Cu-Zn SOD), total antioxidant capacity (T-AOC) and catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST) activities. The expression of nuclear receptors, aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) was declined, down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets in the Cd-treat group. Notably, Se sources application alleviated Cd toxicity by triggering AHR/CAR/PXR/Nrf2 signaling pathway to promote restoring antioxidant defense system and phase I metabolism enzymes system. However, when compared to the effectiveness of antagonism, the nanoparticles of Se were superior in relieving Cd-induced cardiotoxicity via AHR/CAR/PXR/Nrf2 pathway activation than other Se-sources.