DNA damage and repair following In vitro exposure to two different forms of titanium dioxide nanoparticles on trout erythrocyte

TiO(2) has been widely used to promote organic compounds degradation on waste aqueous solution, however, data on TiO(2) nanotoxicity to aquatic life are still limited. In this in vitro study, we compare the toxicity of two different families of TiO(2) nanoparticles on erythrocytes from Oncorhynchus mykiss trout. The crystal structure of the two TiO(2) nanoparticles was analyzed by XRD and the results indicated that one sample is composed of TiO(2) in the anatase crystal phase, while the other sample contains a mixture of both the anatase and the rutile forms of TiO(2) in a 2:8 ratio. Further characterization of the two families of TiO(2) nanoparticles was determined by SEM high resolution images and BET technique. The toxicity results indicate that both TiO(2) nanoparticles increase the hemolysis rate in a dose dependent way (1.6, 3.2, 4.8 μg mL(-1) ) but they do not influence superoxide anion production due to NADH addition measured by chemiluminescence. Moreover, TiO(2) nanoparticles (4.8 μg mL(-1) ) induce DNA damage and the entity of the damage is independent from the type of TiO(2) nanoparticles used. Modified comet assay (Endo III and Fpg) shows that TiO(2) oxidizes not only purine but also pyrimidine bases. In our experimental conditions, the exposure to TiO(2) nanoparticles does not affect the DNA repair system functionality. The data obtained contribute to better characterize the aqueous environmental risks linked to TiO(2) nanoparticles exposure. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2011

Dopaminergic system modulation, behavioral changes, and oxidative stress after neonatal administration of pyrethroids

Pyrethroids are a class of insecticides involved in different neurological disorders. They cross the blood–brain barrier and exert their effect on dopaminergic system, contributing to the burden of oxidative stress in Parkinson’s disease through several pathways. The aim of the present study was to evaluate the effect of neonatal exposition to permethrin and cypermethrin (1/10 of DL50) in rats from the eighth to the fifteenth day of life. Open-field studies showed increased spontaneous locomotor activity in the groups treated with permethrin and the one treated with cypermethrin, while a higher number of center entries and time spent in the center was observed for the cypermethrin-treated group. Lower dopamine and higher homovanillic acid levels were measured in the striatum from both treated groups. A reduction of blood glutathione peroxidase content was measured, while no change in blood superoxide dismutase was observed. Carbonyl group formation increased in striatum, but not in erythrocytes. Lipid peroxidation occurred in erythrocytes, but not in striatum. No changes in fluidity at different depths of plasma membrane were measured in striatum or erythrocytes. The activation of monocyte NADPH oxidase by phorbol esters (PMA) shows that superoxide anion production was reduced in the pyrethroid-treated groups compared to the control group. Our studies suggest that neonatal exposition to permethrin or cypermethrin induces long-lasting effects after developmental exposure giving changes in open-field behaviors, striatal monoamine level, and increased oxidative stress. Although the action of pyrethroids on various target cells is different, a preferential interaction with the extracellular side of plasma membrane proteins can be observed

Metalloporphyrin intercalation in liposome membranes: ESR study

Liposomes characterized by membranes featuring diverse fluidity (liquid-crystalline and/or gel phase), prepared from egg yolk lecithin (EYL) and dipalmitoylphosphatidylcholine (DPPC), were doped with selected metalloporphyrins and the time-related structural and dynamic changes within the lipid double layer were investigated. Porphyrin complexes of Mg(II), Mn(III), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), and the metal-free base were embedded into the particular liposome systems and tested for 350 h at 24°C using the electron spin resonance (ESR) spin probe technique. 5-DOXYL, 12-DOXYL, and 16-DOXYL stearic acid methyl ester spin labels were applied to explore the interior of the lipid bilayer. Only the 16-DOXYL spin probe detected evident structural changes inside the lipid system due to porphyrin intercalation. Fluidity of the lipid system and the type of the porphyrin complex introduced significantly affected the intermolecular interactions, which in certain cases may result in self-assembly of metalloporphyrin molecules within the liposome membrane, reflected in the presence of new lines in the relevant ESR spectra. The most pronounced time-related effects were demonstrated by the EYL liposomes (liquid-crystalline phase) when doped with Mg and Co porphyrins, whereas practically no spectral changes were revealed for the metal-free base and both the Ni and Zn dopants. ESR spectra of the porphyrin-doped gel phase of DPPC liposomes did not show any extra lines; however, they indicated the formation of a more rigid lipid medium. Electronic configuration of the porphyrin’s metal center appeared crucial to the degree of molecular reorganization within the phospholipid bilayer system

Lgl2 Executes Its Function as a Tumor Suppressor by Regulating ErbB Signaling in the Zebrafish Epidermis

Changes in tissue homeostasis, acquisition of invasive cell characteristics, and tumor formation can often be linked to the loss of epithelial cell polarity. In carcinogenesis, the grade of neoplasia correlates with impaired cell polarity. In Drosophila, lethal giant larvae (lgl), discs large (dlg), and scribble, which are components of the epithelial apico-basal cell polarity machinery, act as tumor suppressors, and orthologs of this evolutionary conserved pathway are lost in human carcinoma with high frequency. However, a mechanistic link between neoplasia and vertebrate orthologs of these tumor-suppressor genes remains to be fully explored at the organismal level. Here, we show that the pen/lgl2 mutant phenotype shares two key cellular and molecular features of mammalian malignancy: cell autonomous epidermal neoplasia and epithelial-to-mesenchymal-transition (EMT) of basal epidermal cells including the differential expression of several regulators of EMT. Further, we found that epidermal neoplasia and EMT in pen/lgl2 mutant epidermal cells is promoted by ErbB signalling, a pathway of high significance in human carcinomas. Intriguingly, EMT in the pen/lgl2 mutant is facilitated specifically by ErbB2 mediated E-cadherin mislocalization and not via canonical snail–dependent down-regulation of E-cadherin expression. Our data reveal that pen/lgl2 functions as a tumor suppressor gene in vertebrates, establishing zebrafish pen/lgl2 mutants as a valuable cancer model

Effect of permethrin insecticide on rat polymorphonuclear neutrophils.

Polymorphonuclear neutrophils are professional phagocytes whose efficacy depends on a multicomponent NADPH oxidase for generating superoxide anions and bacterial killing. They can be primed and activated by different agents that can impair oxidative burst and phagocytosis with opposite effects: reduced capability to destroy bacteria or hyperactivation that induces the generation of large quantities of toxic reactive oxygen species, which can damage surrounding tissue and participate in inflammation. The present study was designed to evaluate the effect of sub-chronic (60 days) permethrin treatment (1/10 DL50) on rat polymorphonuclear neutrophils respiratory burst. The results show that permethrin treatment increases superoxide anion production (33 times) and the activity of hydrogen peroxide–myeloperoxidase system (67 times). In vitro experiments suggest that this effect can be related to permethrin priming and to physico-chemical changes at the plasma membrane level of neutrophils. The antioxidant supplementation with Vitamin E and coenzyme Q10 can protect against the abnormal respiratory burst in rat treated with permethrin. The in vitro studies show that neutrophil apoptosis begins soon after 1 h of incubation with permethrin (0.725% of total cells) or its metabolites (3-phenoxybenzyl alcohol, 3-phenoxybenzaldehyde and 3-phenoxybenzoic acid 1.36, 2.26 and 1.3 of total cells, respectively) and that the level of apoptotic cells is very low. In conclusion, immunotoxicity of permethrin measured in rats could prompt future studies on the consequences of chronic insecticide exposure

Radiation Therapy in Acoustic Neuroma

Neuromas or schwannomas of the eighth cranial nerve are benign slow-growing Schwann cell-derived tumors, called acoustic neuromas, or vestibular schwannomas. The incidence is approximately less than 1 per 100,000 persons/ year. Acoustic neuroma has a clinical presentation related to cranial nerve involvement or brainstem and cerebellar compression due to tumor progression. When suspected, clinical diagnosed is confirmed by MRI. The management of vestibular schwannoma is still a quite controversial issue and can include wait and see policy, surgery, and radiotherapy. The treatment choice is based upon the balance between the expected morbidity of the tumor and of the therapy, taking into account also patient\u2019s preference. Medium size (2\u20133 cm) and large tumors (>3 cm) need an active treatment (surgery or radiotherapy), while smaller tumors can undergo observation as an alternative to active treatment.Epidemiology, clinical presentation, diagnosis, and results of the current treatment options including observation, surgery, and radiotherapy will be presented and discussed