Search

Numerous studies have indicated that nano-titanium dioxide (TiO 2 ) can induce neurotoxicity in vitro and in vivo , however, it is unclear whether nano-TiO 2 affects neurite outgrowth of hippocampal neurons. In order to investigate the mechanism of neurotoxicity, rat primary cultured hippocampal neurons on the fourth day of culture were exposed to 5, 15, and 30 μg/mL nano-TiO 2 for 24 h, and nano-TiO 2 internalization, dendritic growth, glutamate metabolism, expression of N-methyl- d -aspartate (NMDA) receptor subunits (NR1, NR2A and NR2B), calcium homeostasis, sodium current (I Na ) and potassium current (I K ) were examined. Our findings demonstrated that nano-TiO 2 crossed the membrane into the cytoplasm or nucleus, and significantly suppressed dendritic growth of primary cultured hippocampal neurons in a concentration-dependent manner. Furthermore, nano-TiO 2 induced a marked release of glutamate to the extracellular region, decreased glutamine synthetase activity and increased phosphate-activated glutaminase activity, elevated intracellular calcium ([Ca 2+ ]i), down-regulated protein expression of NR1, NR2A and NR2B, and increased the amplitudes of the I Na and I K . In addition, nano-TiO 2 increased nitric oxide and nitrice synthase, attenuated the activities of Ca 2+ -ATPase and Na + /K + -ATPase, and increased the ADP/ATP ratio in the primary neurons. Taken together, these findings indicate that nano-TiO 2 inhibits neurite outgrowth of hippocampal neurons by interfering with glutamate metabolism and impairing NMDA receptor function. [ABSTRACT FROM AUTHOR]

Highlights: [•] TiO2 NPs exposure resulted in hippocampus injury and decreased spatial recognition of mice. [•] TiO2 NPs exposure resulted in decreased long-term potentiation. [•] TiO2 NPs exposure caused down-regulation of NR2A and NR2B expression in hippocampus. [•] TiO2 NPs decreased expression of CaMKIV, CREB-1 and FosB/DFosB. [Copyright &y& Elsevier]

Although TiO 2 nanoparticles (NPs) exposure has been demonstrated to cross blood–testis barrier and accumulate in the testis resulting in the reduction of sperm numbers, limited data with respect to the molecular mechanism of decreased spermatogenesis caused by TiO 2 NP exposure. In this research, testicular damage, sperm number and alterations in testis-specific gene expressions in male mice induced by intragastric administration with TiO 2 NPs for six months were investigated. It was found out that TiO 2 NPs could migrate to cells, deposit in the testis and epididymis and thus cause damages to relevant organs, which are, to be more specific, the reductions of total sperm concentrations and sperm motility and an enhancement in the number of abnormal sperms in the cauda epididymis. Furthermore, the individual expression regarding to the mRNAs and proteins of testis-specific genes, including Cdc2, Cyclin B1, Dmcl, TERT, Tesmin, TESP-1, XPD and XRCCI, were significantly declined, whereas Gsk3-β and PGAM4 expressions were greatly elevated in mouse testis due to the exposures, which in fact implied that the reduced spermatogenesis may be involved in the alternated testis-specific gene expressions in those exposed male mice. [ABSTRACT FROM AUTHOR]

Highlights: [•] Phoxim exposure resulted in decrease of the cocooning rate of B. mori. [•] TiO2 NPs could increase the cocooning rate of B. mori under phoxim toxicity. [•] Phoxim exposure damaged silk gland and decreased Fib-L, Ser2, Ser3, and P25 expressions. [•] TiO2 NPs could relieve silk gland damage and increase Fib-L, Ser2, Ser3, and P25 expressions. [Copyright &y& Elsevier]

Highlights: [•] Exposure to TiO2 NPs could cross blood–testis barrier and be accumulated in testis. [•] Exposure to TiO2 NPs caused testis and sperm lesions in male mice. [•] Exposure to TiO2 NP decreased sperm numbers and sperm motility in male mice. [•] Exposure to TiO2 NP resulted in imbalance of sex hormones in male mice. [•] Exposure to TiO2 NP caused alteration of 142 genes expression of known function in testis. [ABSTRACT FROM AUTHOR]

Abstract: Numerous studies have demonstrated that the brain is one of the target organs in acute or chronic titanium dioxide (TiO2) nanoparticles (NPs) toxicity, and oxidative stress plays an important role in this process. However, whether brain oxidative injury responds to TiO2 NPs by activating the P38-nuclear factor-E2-related factor-2 (Nrf-2) pathway is not fully understood. The present study aimed to examine activation of the P38-Nrf-2 signaling pathway associated with oxidative stress in the mouse brain induced by intranasal administration of TiO2 NPs for 90 consecutive days. Our findings indicate that TiO2 NPs caused overproliferation of spongiocytes and hemorrhage in the mouse brain. Furthermore, TiO2 NPs significantly activated p38, c-Jun N-terminal kinase, nuclear factor kappa B, Nrf-2 and heme oxygenase-1 expression in the brain, which in turn, led to increased production of reactive oxygen species, as well as lipid, protein and DNA peroxidation. These findings suggest that TiO2 NPs-induced oxidative damage in the mouse brain may occur via the p38-Nrf-2 signaling pathway. Therefore, application of TiO2 NPs in the environment should be performed with caution. [Copyright &y& Elsevier]

Abstract: Although numerous studies have described the accumulation of titanium dioxide nanoparticles (TiO2 NPs) in the liver, kidneys, lung, spleen, and brain, and the corresponding damage, it is unclear whether or not TiO2 NPs can be translocated to the ovary and cause ovarian injury, thus impairing fertility. In the current study, ovarian injury and gene-expressed characteristics in female mice induced by intragastric administration of TiO2 NPs (10mg/kg) for 90 consecutive days were investigated. Our findings indicated that TiO2 NPs can accumulate in the ovary and result in ovarian damage, cause an imbalance of mineral element distribution and sex hormones, decrease fertility or the pregnancy rate and oxidative stress in mice. Microarray analysis showed that in ovaries from mice treated with TiO2 NPs compared to controls, 223 genes of known function were up-regulated, while 65 ovarian genes were down-regulated. The increased expression of Cyp17a1 following TiO2 NPs treatment suggested that the increase in estradiol biosynthesis may be a consequence of increased TiO2 NPs. In addition, the elevated expression of Akr1c18 implied that progesterone metabolism was accelerated, thus causing a decrease in the progesterone concentration. Taken together, the apparent regulation of key ovarian genes supports the hypothesis that TiO2 NPs directly affects ovarian function. [Copyright &y& Elsevier]

Abstract: Exposure to titanium dioxide nanoparticles (TiO2 NPs) has been demonstrated to result in pulmonary inflammation in animals; however, very little is known about the molecular mechanisms of pulmonary injury due to TiO2 NPs exposure. The aim of this study was to evaluate the oxidative stress and molecular mechanism associated with pulmonary inflammation in chronic lung toxicity caused by the intratracheal instillation of TiO2 NPs for 90 consecutive days in mice. Our findings suggest that TiO2 NPs are significantly accumulated in the lung, leading to an obvious increase in lung indices, inflammation and bleeding in the lung. Exposure to TiO2 NPs significantly increased the accumulation of reactive oxygen species and the level of lipid peroxidation, and decreased antioxidant capacity in the lung. Furthermore, TiO2 NPs exposure activated nuclear factor-κB, increased the levels of tumor necrosis factor-α, cyclooxygenase-2, heme oxygenase-1, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, and CYP1A1 expression. However, TiO2 NPs exposure decreased NF-κB-inhibiting factor and heat shock protein 70 expression. Our results suggest that the generation of pulmonary inflammation caused by TiO2 NPs in mice is closely related to oxidative stress and the expression of inflammatory cytokines. [Copyright &y& Elsevier]