| The lanthanide series of elements (Ln) comprise 15 trivalent metallic elements in the periodic table, plus yttrium and scandium, also known as rare earth elements (REEs). For their special 4f electronic configuration and similarity with Ca2+, REEs are mainly used in industry and medicine. China provides the most of worldwide REEs supply. And The REEs applied in agriculture originated with China for REEs fertilizer or additive could promote crop production and animal growth. With the increasing and continued use, this group of biologically non–necessary elements was inevitably accumulated in environment and then transfer to human body through food chain. Therefore the toxic studies of REEs on animal had been carried out for many years. However, the effects of REEs on immune organ such as spleen and immune system were seldom studied. Furthermore, previous studies on biological effect of REEs always concentrated on single REE or REEs compounds, the studies on the different biological effect caused by different REE were few. Thus we chose lanthanum (La), cerium (Ce) and neodymium (Nd) which are the main components of REEs fertilizers to treat male ICR mice by intraperitoneal injection or by gavage, respectivily, studying the injury mechanism of the mouse spleen caused by REEs, the effect of REEs on immunity and liver function in mice, and the effect of REEs ion on the enzyme protein, trying to understand the biological effect of REEs from the levels of whole animal body, tissues cells and molecule. Our study also offers a reference for the safety evaluation of the REEs application.Three main aspects are involved.(1) The splenic injury in mice caused by Ln was studied, and various biochemical and chemical parameters were assayed in the mouse spleen. Abdominal exposure to LaCl3, CeCl3, and NdCl3 caused splenomegaly and oxidative stress to the spleen. Evident Ln deposition, congestion, mitochondria swelling, and apoptosis in the spleen could be observed, followed by increased generation of reactive oxygen species, lipid peroxidation and SOD activity, and decreased GSH–Px activity as well as nonenzymatic antioxidants such as glutathione and ascorbic acid content. In addition, the high amount of NO and increased NOS activities caused by Ln were measured. It was implied that spleen was the target injuried organ for Ln by intraperitoneal injection. Furthermore, both Ce3+ and Nd3+ exhibited higher oxidative stress and toxicity on spleen than La3+, and Ce3+ caused more serve splenocyte injuries and oxidative stress than Nd3+, implying that the difference in the splenic injuries caused by Ln was related to the number of 4f electrons of Ln.(2) The effects of subchronic exposure to Ln on various organs and serum biochemical parameters in mice were studied. The results showed that that Ln increased the coefficients of spleen, thymus and liver. The assay of serum biochemical parameters demonstrated that Ln injuried myocardium, liver and kidney function. The liver slices indicated that Ln also caused liver tissue injury. It was suggested that Ln had adverse effect on various organ and disrupt normal function of some important organs such as myocardium, liver and kidney. The assay of serum biochemical parameters demonstrated that the damage of liver, kidney and myocardium function caused by Ce3+ was most severe, medium in Nd3+ treatment, and least in La3+ treatment.(3) The effects of long–term exposure to Ln on immunity and liver function of mice were studied. The results showed that the effects of Ln on mice were dose–dependent: the effects of low dose were slight while the middle and high doses displayed more significant effects, e.g. Ln3+ at higher doses inhibited the number of T, B lymphocytes and NK cell in the peripheral blood, decreasing the blood cell counts such as white blood cells, platelets and reticulocytes and the serum IgM level in mice. Furthermore, liver function was damaged, glucose and lipid metabolism were disrupted, liver pathological structure and spleen ultrasructure were changed. Comparing with middle dose, high dose Ln inhibited mice growth. It demonstrated that long–term exposure to Ln affected the cellular and humoral immunity and disturbed liver function of mice which might have adverse effect on whole body of mice. Among the three various Ln ions treatments, Ce3+ exhibited the most significant injuried effects, next came Nd3+ and La3+, respectively.From all the results above, it was implied that the different biological effects caused by Ln was related to the number of 4f electrons of Ln.(4) Ce3+ in various concentrations was added to superoxide dismutase (SOD) from rat eryhrocyte in vitro to gain insight into the mechanism of molecular interactions between Ce3+ and SOD. The results showed that the reaction between SOD and Ce3 was two–order, which meant that the SOD activity was markedly accelerated by low concentration of Ce3+ and inhibited by high concentration of Ce3+. The spectroscopic assays suggested that the Ce3+ was determined to directly bind to SOD; the binding site of Ce3+ to SOD was 0.96 and the binding constants (KA) were 6.78×105 L?mol-1 and 1.68×105 L?mol-1; the binding Ce3+ entirely altered the secondary structure of SOD. It implied that the Ce3+ coordination created a new metal ion-active site form in SOD, thus leading to an enhancement in SOD activity.
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