Investigate The Immunotoxicity Of Macrophages Mediated By Cadmium Contamination In Food And The Mechanism Of Selenium Antagonism

Food is the most important item to people,so food safety is the highest priority.On the subject of food safety,exposure to cadmium through food has become a hot topic.The results demonstrated that cadmium pollution ingested through food might accumulate in immune cells,thereby impairing immune function and posing a threat to human health.Macrophages,an essential component of the immune system,can be classified as M1 type or M2 type,with M1 type macrophages exhibiting pro-inflammatory,bactericidal,and anti-tumour activities.There is no effective remedy for dietary cadmium exposure at the moment.Studies have demonstrated that selenium efficiently counteracts the toxicity of cadmium,although the underlying mechanism has not been explored.We investigated the effect and mechanism of selenium on the cadmium-induced immunotoxicity of macrophages by establishing a model of cadmium poisoning.Methods:In this work,M1 macrophages were employed to generate a cadmium poisoning model to examine the immunotoxicity of selenium on macrophages produced by cadmium.The CCK-8,light microscopy observation,and qRT-PCR were used to examine the influence of selenium on the toxicity and immune regulatory factors caused by cadmium in macrophage development.Flow cytometry was used to detect the energy metabolism of cadmium-poisoned macrophages;selenium inhibited the energy metabolism of cadmium-poisoned macrophages;and GC-MS was used to detect the changes in metabolites,revealing the immunotoxic mechanism of selenium on cadmium-induced macrophages.Results:(1)Compared to the control group,cadmium exposure decreased the survival rate of M1 macrophages in a dose-dependent way(p<0.05).There was a change in cell shape,expansion and contraction of the intercellular gap,and cell loss.Selenium might increase Ml macrophages’survival rate(p<0.05).Compared to the cadmium treatment group,the survival rate of M1 type macrophages in the cadmium-antagonistic selenium group was considerably higher(p<0.05),as were the number of cells and intercellular space.These results demonstrated that macrophages of the M1 subtype were susceptible to cadmium-induced growth toxicity and that selenium might reduce this toxicity.(2)The mRNA expression levels of IL-1,IL-6,IFN-β,TNF-α,MIPla,and COX-2 in Ml type macrophages of the cadmium treatment group were significantly decreased(p<0.05),suggesting that cadmium could inhibit the production of pro-inflammatory cytokines and reduce the immune regulation of M1 type macrophages.The mRNA expression levels of IFN-β,TNF-α,MIPla,and COX-2 in M1 type macrophages of the selenium treatment group were substantially elevated(p<0.05),indicating that selenium may boost the production of pro-inflammatory cytokines and enhance the immunological modulation of Ml type macrophages.Compared to the cadmium treatment group,selenium inhibited the significantly elevated mRNA expression levels of IL-1,IL-6,IFN-β,TNF-α,MIP-1α,and COX-2 in M1 type macrophages(p<0.05),indicating that selenium could enhance the immunoregulatory function of M1 type macrophages by promoting the production of pro-inflammatory factors,thereby inhibiting cadmium-mediated immunotoxicity.(3)Cadmium treatment reduced greatly the glycolysis and glucose reliance of M1 type macrophages and raised the amount of oxidative phosphorylation and the oxidation capacity of fatty acids and amino acids in a dose-dependent manner(p<0.05).Selenium enhanced the glycolysis and glucose reliance of macrophages of the M1 type and decreased the oxidative phosphorylation level and the oxidation capacity of fatty acids and amino acids in a dose-dependent manner(p<0.05).In comparison to the cadmium treatment group,the antagonism of selenium to cadmium greatly enhanced the glycolysis and glucose reliance of M1 type macrophages and dramatically decreased the amount of oxidative phosphorylation and the oxidation capacity of fatty acids and amino acids(p<0.05).These findings showed that selenium prevented the immunotoxicity caused by cadmium exposure and restored the normal immunomodulatory actions of Ml-type macrophages by boosting glycolysis and decreasing oxidative phosphorylation.(4)Cadmium exposure primarily promotes the breakdown of arginine into L-proline by inhibiting glycolysis,fatty acid production,and glutathione metabolism,therefore decreasing the pro-inflammatory action of Ml-type macrophages and severely impacting their immunological function.Selenium suppresses the breakdown of arginine into L-proline by boosting glycolysis,fatty acid production,and glutathione metabolism,therefore reducing the immunotoxicity induced by cadmium exposure and restoring the normal immunological regulation of M1-type macrophages.In conclusion,selenium can effectively inhibit the immunotoxicity of cadmium and alleviate the cadmium-mediated immunotoxicity by enhancing the pro-inflammatory function of Ml-type macrophages,providing a novel concept for the development of effective nutritional supplements to reduce the toxicity of food-derived cadmium.