Selenium Antagonizes Cadmium-Induced Inflammation and Oxidative Stress via Suppressing the Interplay between NLRP3 Inflammasome and HMGB1/NF-κB Pathway in Duck Hepatocytes

Abstract

Cadmium (Cd) is a toxic heavy metal that can accumulate in the liver of animals, damaging liver function. Inflammation and oxidative stress are considered primary causes of Cd-induced liver damage. Selenium (Se) is an antioxidant and can resist the detrimental impacts of Cd on the liver. To elucidate the antagonism of Se on Cd against hepatocyte injury and its mechanism, duck embryo hepatocytes were treated with Cd (4 μM) and/or Se (0.4 μM) for 24 h. Then, the hepatocyte viability, oxidative stress and inflammatory status were assessed. The findings manifested that the accumulation of reactive oxygen species (ROS) and the levels of pro-inflammatory factors were elevated in the Cd group. Simultaneously, immunofluorescence staining revealed that the interaction between NOD-like receptor pyran domain containing 3 (NLRP3) and apoptosis-associated speck-like protein (ASC) was enhanced, the movement of high-mobility group box 1 (HMGB1) from nucleus to cytoplasm was increased and the inflammatory response was further amplified. Nevertheless, the addition of Se relieved the above-mentioned effects, thereby alleviating cellular oxidative stress and inflammation. Collectively, the results suggested that Se could mitigate Cd-stimulated oxidative stress and inflammation in hepatocytes, which might be correlated with the NLRP3 inflammasome and HMGB1/nuclear factor-κB (NF-κB) signaling pathway.

Rutin Nanoparticles Alleviate Cadmium-Induced Oxidative and Immune Damage in Broilers’ Bursa of Fabricius via Modulating Hsp70/TLR4/NF-κB Signaling Pathway

“…In the present study, our molecular and immunohistochemical findings revealed that the Cd-intoxicated group markedly upregulates the expression level of HSP70, TLR4, and NF-κB. These findings come in agreement with [123] who reported that Cd significantly promoted the expression level of the TLR4/NF-κB pathway in duck embryo hepatocytes, and also [124], exhibited that Cd enhanced the expression of HMGB1 downstream mediators, including TLR-4 and NF-κB which exacerbated the damaging effects of Cd in exposed tissues via stimulating the release of several inflammatory cytokines. Interestingly [125], revealed that Cd could induce adrenal damage through activation of TLR4/ NF-κB-mediated inflammatory responses which play an essential role in Cd-induced toxic lesions.…”

Selenium and zinc alleviate hepatotoxicity induced by heavy metal mixture (cadmium, mercury, lead and arsenic) via attenuation of inflammo‐oxidant pathways

“…Oxidative stress, inflammatory process, apoptosis and antioxidation system could interact (Table 4). ROS leads to oxidative stress which could activate the inflammatory pathways, and in turn will positively lead to further generation of ROS 67 . Studies have shown that HM's like Pb, Cd, or As could generate ROS, lead to oxidative stress and subsequent activation of the inflammatory and apoptotic processes 1,3,5,51 .…”

“…ROS leads to oxidative stress which could activate the inflammatory pathways, and in turn will positively lead to further generation of ROS. 67 Studies have shown that HM's like Pb, Cd, or As could generate ROS, lead to oxidative stress and subsequent activation of the inflammatory and apoptotic processes. 1,3,5,51 These interactive effects manifested in our correlation studies.…”