Yuguan Ze

Renal Injury and Nrf2 Modulation in Mouse Kidney Following Chronic Exposure to TiO2 Nanoparticles

TiO₂ nanoparticles (NPs) are used in the food industry but have potential toxic effects in humans and animals. TiO₂ NPs impair renal function and cause oxidative stress and renal inflammation in mice, associated with inhibition of nuclear factor erythroid-2-related factor 2 (Nrf2), which regulates genes encoding many antioxidants and detoxifying enzymes. This study determined whether TiO₂ NPs activated the Nrf2 signaling pathway. Mice exhibited accumulation of reactive oxygen species and peroxidation of lipid, protein, and DNA in the kidney, coupled with renal dysfunction, glutathione depletion, inflammatory cell infiltration, fatty degeneration, and apoptosis. These were associated with increased expression of NOX4, cyclooxygenase-2, and nuclear factor-κB. Oxidative stress and inflammation were accompanied by decreased expression of Nrf2 and down-regulation of its target gene products including heme oxygenase 1, glutamate-cysteine ligase catalytic subunit, and glutathione S-transferase. Chronic TiO₂ NP exposure is associated with suppression of Nrf2, which contributes to the pathogenesis of oxidative stress and inflammation.

Toxicological Mechanisms of Nanosized Titanium Dioxide-Induced Spleen Injury in Mice after Repeated Peroral Application

Due to an increase in surface area per particle weight, nanosized titanium dioxide (nano-TiO2) has greatly increased its function as a catalyst and is used for whitening and brightening foods. However, concerns over the safety of nano-TiO2 have been raised. The purpose of this study was to determine whether the protein kinase MAPKs/PI3-K/Akt signaling pathways and transcription factors are activated prior to or concurrent with COX-2 up-regulation in mouse spleen following exposure to 10 mg/kg BW of pure anatase nano-TiO2 by the intragastric route for 15-90 days. The study clearly showed that nano-TiO2 was deposited in the spleen and resulted in reactive oxygen species production, time-dependent splenic inflammation, and necrosis, coupled with a 12.64-64.06% increase in COX-2 and prostaglandin E2 expression, respectively. Furthermore, nano-TiO2 elevated the expressions of ERK, AP-1, CRE, Akt, JNK2, MAPKs, PI3-K, c-Jun, and c-Fos in the spleen by 1.08-6-fold with increased exposure duration, respectively. These findings suggested that nano-TiO2-induced COX-2 expression may be mediated predominantly through the induction of AP-1 and CRE and that AP-1/CRE induction occurred via the MAPKs/PI3-K/Akt signaling pathways in the spleen. Therefore, the findings suggest the need for caution when using nanomaterials as food additives.

Cerium Relieves the Inhibition of Nitrogen Metabolism of Spinach Caused by Magnesium Deficiency

Magnesium is one of the essential elements for plant growth and cerium is a beneficial element for plant growth. However, the effects of the fact that cerium improves the nitrogen metabolism of plants under magnesium deficiency is poorly understood. The main aim of the study was to determine the role of cerium in the amelioration of magnesium-deficiency effects in spinach plants. Spinach plants were cultivated in Hoagland’s solution. They were subjected to magnesium deficiency and to cerium chloride administered in the magnesium-present media and magnesium-deficient media. Spinach plants grown in the magnesium-present media and magnesium-deficient media were measured for key enzyme activities involved in nitrogen metabolism such as nitrate reductase, nitrite reductase, glutamate dehydrogenase, glutamate synthase, urease, glutamic–pyruvic transaminase, and glutamic–oxaloace protease transaminase. As the nitrogen metabolism in spinach was significantly inhibited by magnesium deficiency, it caused a significant reduction of spinach plant weight, leaf turning chlorosis. However, cerium treatment grown in magnesium-deficiency media significantly promoted the activities of the key enzymes as well as the contents of the free amino acids, chlorophyll, soluble protein, and spinach growth. It implied that Ce3+ could partly substitute for magnesium to facilitate the transformation from inorganic nitrogen to organic nitrogen, leading to the improvement of spinach growth, although the metabolism needs to be investigated further.

Influences of magnesium deficiency and cerium on antioxidant system of spinach chloroplasts

Magnesium-deficiency conditions applied to spinach cultures caused an oxidative stress status in spinach chloroplast monitored by an increase in reactive oxygen species (ROS) accumulation. The enhancement of lipids peroxide of spinach chloroplast grown in magnesium-deficiency media suggested an oxidative attack that was activated by a reduction of antioxidative defense mechanism measured by analysing the activities of superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and glutathione reductase, as well as antioxidants such as carotenoids and glutathione content. As the antioxidative response of chloroplast was reduced in spinach grown in magnesium-deficiency media, it caused a significant reduction of spinach plant weight, old leaves turning chlorosis. However, cerium treatment grown in magnesium-deficiency conditions decreased the malondialdehyde and ROS, and increased activities of the antioxidative defense system, and improved spinach growth. Together, the experimental study implied that cerium could partly substitute for magnesium and increase the oxidative stress-resistance of spinach chloroplast grown in magnesium-deficiency conditions, but the mechanisms need further study.

Improvement of cerium on photosynthesis of maize seedlings under a combination of potassium deficiency and salt stress.

Added Ce3+ can partly substitute for Ca2+ or Mg2+ and improve photosynthesis under the deficiency of these elements, but very few studies focused on photosynthetic improvement in maize seedlings caused by K+ deficiency, salt stress, especially a combination of K+ deficiency and salt stress. In the present study, the effects of Ce3+ on the photosynthesis of maize seedlings under the three different stresses were investigated. The results showed that added Ce3+ under various stresses increased the ratios of free water/bound water and of K+/Na+, the pigment contents, the values of Fv/Fm, Y(II), ETR(II), Y(NPQ), Qp, qL, NPQ, and qN of photosystem II (PSII), the values of Y(I) and ETR(I) of photosystem I (PSI) and the expression levels of LhcII cab1 and rbcL, and decreased the values of Y(NO) and Y(NA). This implied that added Ce3+ depressed ion toxicity, photodamage of PSII, and acceptor side constraints of PSI, and enhanced adjustable energy dissipation, the responses of photochemistry, and carbon assimilation caused by K+ deficiency, salt stress, and the combination of K+ deficiency and salt stress. However, Ce3+ mitigation of photosynthetic inhibition in maize seedlings caused by the combined stresses was greater than that of salt stress, and Ce3+ mitigation under salt stress was greater than that under K+ deficiency. In addition, the results also showed that Ce3+ cannot improve photosynthesis and growth of maize seedlings under K+ deficiency by substituting for K+.

Hippocampal Damage and Alterations of Inflammatory Cytokine Expression in Mice Caused by Exposure to Cerium Chloride

Rare earth element (REE) exposure has been shown to induce central nerve system intoxication, but the molecular mechanisms by which this occurs are poorly understood. In this study, cerium (Ce), in the form of CeCl3, was administered by way of gavage to mice for 90 consecutive days, and cytokine expression, associated with neuroinflammation of hippocampus, as well as spatial memory were increased in mice. Significant Ce accumulation in hippocampus, which led to neuroinflammation and decreased spatial memory of mice, was observed. Furthermore, CeCl3 remarkably increased levels of Toll-like receptors 2 and 4, tumor necrosis factor-α, nucleic IκB kinase, factor-κB–inducible kinase, nucleic factor-κB, and p52 and p65 expression as well as significantly decreased levels of IκB and interleukin-2 expression. These results showed that neuroinflammation and damaged hippocampal function may be associated with CeCl3-induced neuerotoxicity. Our findings suggest the need for workers and consumers to exercise caution when handling REEs.

The Impairment of Liver DNA Conformation and Liver Apoptosis of Mice Caused by CeCl3

Cerium (Ce) was shown to cause various toxic effects both in rats and mice; however, the molecular mechanism by which Ce exert theirs toxicity is still understood. In this report, the impairment of liver DNA conformation and liver apoptosis of mice caused by CeCl3 was studied in vivo using inductively coupled plasma–mass spectrometry, various spectral methods, gel electrophoresis, and transmission electron micrograph. We found that the coefficients of liver to body weight of the mice treated with CeCl3 were significantly increased. Ce3+ could be significantly accumulated in the liver, and it insert itself into DNA base pairs and/or bind to DNA nucleotide, and alter the conformation of DNA. Furthermore, the evaluation by gel electrophoresis and transmission electron micrograph showed that higher dose of Ce3+ could cause DNA cleavage and hepatocyte apoptosis in mice. Therefore, our study aroused the attention of Ce application and exposure effects especially on human liver for long-term and low-dose treatment.