Selenium triggers Nrf2-mediated protection against cadmium-induced chicken hepatocyte autophagy and apoptosis.

Cadmium (Cd) is a ubiquitously distributed trace metal and environmental pollutant that is highly toxic to liver. Selenium (Se) may provide chemoprotection against Cd-induced cytotoxicity by augmenting the cellular antioxidant capacity. However, the mechanism of Se chemoprotection against Cd-induced hepatotoxicity is unclear. The present study evaluated the ameliorative properties of Se against Cd-induced cytotoxicity in hepatocytes. Primary cells were exposed to 5μM Cd and/or 1μM Se for 24h. Cellular morphology and function, antioxidant status, activation of Nrf2 pathway, autophagy and apoptosis were determined. These results indicated that Se ameliorated the cytotoxicity of Cd by recovering hepatocyte morphology and function, inhibiting reactive oxygen species (ROS) and malondialdehyde (MDA) production, reducing intracellular LDH release, autophagy and apoptosis, and increasing the major antioxidative activities (Total antioxidant capacity (T-AOC) and superoxide dismutase (SOD). In summary, Cd is a hepatotoxin that causes hepatocytes damage by inducing oxidative stress, excessive autophagy and apoptosis as a mechanism of toxicity. Moreover, Se supplement ameliorated these effects by enhancing antioxidant systems, decreasing excessive autophagy and apoptosis. These results suggested that Se triggers Nrf2-mediated protection as the mechanism of Se chemoprotection against Cd-induced autophagy and apoptosis.

Zhang C ，Lin J ，Ge J ，Wang LL ，Li N ，Sun XT ，Cao HB ，Li JL ... -  《-》

Selenium antagonizes cadmium-induced apoptosis in chicken spleen but not involving Nrf2-regulated antioxidant response.

The nuclear transcription factor NF-E2-related factor 2 (Nrf2) binds to antioxidant response elements (AREs) and is involved in the regulation of genes participated in defending cells against oxidative damage, which have been confirmed in animal models. Selenium (Se), known as an important element in the regulation of antioxidant activity, can antagonize Cadmium (Cd) toxicity in birds. However, the role of Nrf2 in selenium-cadmium interaction has not been reported in birds. To further explore the mechanism of selenium attenuating spleen toxicity induced by cadmium in chickens, cadmium chloride (CdCl2, 150mg/kg) and sodium selenite (Na2SeO3, 2mg/kg) were co-administrated or individually administered in the diet of chickens for 90 days. The results showed that Cd exposure increased the level of hydrogen peroxide (H2O2) and malondialdehyde (MDA) and decreased the antioxidant enzyme activities, including superoxide dismutase (SOD), glutathione peroxidase (Gpx), total antioxidative capacity (T-AOC), catalase (CAT). Cd exposure increased obviously nuclear accumulation of Nrf2, and the expression of Nrf2 downstream heme oxygenase-1 (HO-1) and NAD(P)H: quinine oxidoreductase 1 (NQO1), reduced the expression of Kelch-like ECH-associated protein (keap1), Gpx-1 and thioredoxin reductase-1 (TrxR1). In addition, Cd induced the increase of bak, caspase9, p53, Cyt c mRNA levels, increased bax/bcl-2 ratio, increased caspase3 mRNA and protein levels. Selenium treatment reduced the accumulation of Cd in the spleen, attenuates Cd-induced Nrf2 nuclear accumulation, enhanced antioxidant enzyme activities, ameliorated Cd-induced oxidative stress and apoptosis in the spleen. In summary, our results demonstrate that Se ameliorated spleen toxicity induced by cadmium by modulating the antioxidant system, independently of Nrf2-regulated antioxidant response pathway.

Chen M ，Li X ，Fan R ，Cao C ，Yao H ，Xu S ... -  《-》

The Protective Effect of Selenium on the Chicken Pancreas against Cadmium Toxicity via Alleviating Oxidative Stress and Autophagy.

Liu R ，Jia T ，Cui Y ，Lin H ，Li S ... -  《-》

Isoliquiritigenin in licorice functions as a hepatic protectant by induction of antioxidant genes through extracellular signal-regulated kinase-mediated NF-E2-related factor-2 signaling pathway.

Park SM ，Lee JR ，Ku SK ，Cho IJ ，Byun SH ，Kim SC ，Park SJ ，Kim YW ... -  《-》

Sulforaphane Protect Against Cadmium-Induced Oxidative Damage in mouse Leydigs Cells by Activating Nrf2/ARE Signaling Pathway.

Yang SH ，Li P ，Yu LH ，Li L ，Long M ，Liu MD ，He JB ... -  《INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES》