Oxidative injury in the mouse spleen caused by lanthanides

doi:10.1016/j.jallcom.2009.09.158

Journal of Alloys and Compounds

Volume 489, Issue 2, 21 January 2010, Pages 708-713

https://doi.org/10.1016/j.jallcom.2009.09.158 Get rights and content

Abstract

The organ-toxicity of high-dose lanthanides on organisms had been recognized, but very little is known about the injury of immune organ such as spleen induced by Ln. In order to understand the splenic toxicity of Ln, various biochemical and chemical parameters were assayed in the mouse spleen. Abdominal exposure to LaCl₃, CeCl₃, and NdCl₃ at dose of 20 mg/kg body weight 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. 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.

Introduction

With their widespread application in agriculture, industry, culture, medicine, and daily life, lanthanides (Ln) compounds are being brought into the ecological environment and human body through food chains [1], [2], [3]. It is important to know the acute and chronic effects of Ln on the environment, nature balance, and the human body after their entry into bodies and the environment. The studies on the toxicology of Ln showed that lanthanide ions (Ln³⁺) had adverse effects on organs such as the liver, kidney and lung as well as the nervous system of animals, e.g., the lesion caused by Ln showed oxidative stress, disturbance of the homeostasis of essential elements and enzymes as well as histopathological changes [4], [5], [6], [7], [14]. However, the studies focused the biological and toxic effects of Ln primarily on single Ln and their mixtures in animals. In the study of the effects on vigor of aged spinach seeds caused by LaCl₃, CeCl₃ and NdCl₃, Liu et al. showed that the effects of Ce³⁺ were most significant, then followed by Nd³⁺ while La³⁺ was not as effective as Ce³⁺ and Nd³⁺ [8]. Li et al. found an increase in ketone bodies, creatinine, lactate, succinate and various amino acid in the serum of rats intraperitoneally exposed to La³⁺ and Ce³⁺ at doses of 10 and 50 mg/kg body weight after 48 h by MAS ¹H NMR spectroscopic-based metabonomic approach, together with a decrease in glucose in the serum from Ce³⁺-treated groups, thus they thought that both La³⁺ and Ce³⁺ at high doses impaired the specific region of liver and Ce³⁺ exhibited a higher toxicity than La³⁺ at the same dose [9]. Liao et al. also demonstrated that Ce³⁺ caused lesions on liver and kidney in rats while La³⁺ only caused liver injury at the same dose [10], and Nd³⁺ had similar acute toxicity to Ce³⁺ [11]. These studies suggested that La³⁺, Ce³⁺ and Nd³⁺ had different biological effects on organisms and Ce³⁺ or Nd³⁺ had a stronger effect than La³⁺ at the same dose.

As we know, Ln belong to the IIIB family in the periodic table of elements. The special electronic configuration in Ln is the occupation of 4f orbitals: the outer-shell 5s, 5p and 6s orbitals are occupied completely in the closed-shell (no electron or only one electron in 5d orbital); while the inner-shell seven 4f-orbitals are occupied one by one incompletely in the open shell according to the increase of the atomic number (0–14). And all Ln form stable triple-charged state when they lose outer electrons and the electron configuration of Ln³⁺ ions extends from f⁰ (La³⁺) to f¹⁴ (Lu³⁺) regularly. Thus La³⁺ has no f electron, Ce³⁺ has one and Nd³⁺ has three f electron, respectively. Moreover, according to the Hund's rule, the empty (f⁰), half-filled (f⁷) and the completely filled shell (f¹⁴) are in stable state. So Ce³⁺ (f¹) can easily lose an electron to be oxidized to Ce⁴⁺ (f⁰) [1], [12], [13]. Ln as the 4f group elements varied only in the number of 4f electrons, their chemical properties are similar. Based on the small amount of available data, Kostova et al. proposed that the difference in the number of 4f electrons leads to quite different biological properties of Ln [15]. Do Ln behave differently in biological effects determined by the 4f electron? It deserves to be investigated. In addition, the previous studies on bio-toxicity of Ln were generally concentrated on organs such as lung, liver, and kidney and suggested that the damages were related to the oxidative stress caused by Ln [5], [14], [16]. The researches on splenic toxicity of Ln are rarely reported. Spleen is the largest immune organ in humans, participating in immune response, generating lymphocytes, eliminating aging erythrocytes and storing blood. Is the bio-toxicity of Ln on spleen also related to the oxidative injuries? The Ln-induced toxicity on spleen needs investigation.

In this paper, spleen indices, the deposition of Ln, the changes of histopathological and cellular ultrastructure, the level of nitric oxide and nitric oxide synthase as well as antioxidant system in the mouse spleen were investigated to understand the splenic injury in mice caused by Ln.

Section snippets

Reagent

LaCl₃, CeCl₃, and NdCl₃ were purchased from Shanghai Chem. Co. and were analytical-grade.

Animals and treatment

Male CD-1 (ICR) mice (∼25 g) were obtained from the Animal Center of Soochow University, Suzhou, China. They were 4–6 weeks old upon arrival and allowed to acclimatize in an environment-controlled animal room (temperature, 26 ± 1 °C; relative humidity, 50 ± 5%; photoperiod, 12 h light/dark cycle) for 7 days prior to treatment. Distilled water and sterilized food were provided ad libitum. All animal procedures were

Body weight and spleen indices in mice

During the treatment, animals were all at growth state. The daily behaviors such as feeding, drinking and activity in Ln³⁺-treated groups were as normal as the control group. Table 1 shows the weight gain and spleen indices of mice after the 14-day administration. The weight gain of mice by Ln³⁺ treatments were lower than the control, but the differences were not statistically significant (p > 0.05). The spleen indices in Ln³⁺-treated groups was significantly higher than the control (p < 0.001),

Discussion

In this experiment the mice growth was not obviously inhibited by Ln³⁺ at dose of 20 mg/kg, while the spleen is clearly sensitive to Ln action, where an increase in spleen weight/body weight ratio took place. Liu et al. indicated that the ratios of spleen to body weight of rats or mice were not modified after feeding mixture of La(NO₃)₃ and Ce(NO₃)₃ by oral administration for a month compared with the control [24], [25]. As nonessential metal elements, overdose Ln³⁺ entering abdominal cavity

Conclusion

Our study demonstrated that abdominal exposure to La³⁺, Ce³⁺, and Nd³⁺ at dose of 20 mg/kg BW for 14 days caused evident deposition of Ln, increased spleen indices, histopathological changes and ultrastructure lesion as well as oxidative stress in the mouse spleen. Among the three treatments, the Ce³⁺-treated group exhibited the most severe splenic injury and oxidative stress, next was the Nd³⁺-treated group, and than the La³⁺-treated group. The difference of splenic injuries caused by Ln³⁺ was

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Grant No. 30901218), the Medical Development Foundation of Soochow University, Suzhou, China (Grant No. EE120701) and the National Bringing New Ideas Foundation of Student of China (Grant Nos. 57315427, 57315927).

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¹: These authors contributed equally to this work.

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Oxidative injury in the mouse spleen caused by lanthanides

Abstract

Introduction

Section snippets

Reagent

Animals and treatment

Body weight and spleen indices in mice

Discussion

Conclusion

Acknowledgements

Toxicol. Lett.

Life Sci.

J. Mol. Struct-Theochem

Toxicol. Lett.

J. Trace Elem. Med. Biol.

J. Inorg. Biochem.

Method Enzymol.

Anal. Biochem.

Cell Calcium

Alloy Compd.

J. Trace Elem. Med. Biol.

J. Mol. Cell. Cardiol.

J. Orthop. Res.

Chem-Biol. Interact.

Chem. Rev.

Int. Dairy J.

Bioinorganic Chemistry of Rare Earth Elements

The Introduction to Rare Earth

Biochemistry of the Lanthanides

J. Rare Earth

J. Rare Earth