Tania García

Oxidative stress status and RNA expression in hippocampus of an animal model of Alzheimer's disease after chronic exposure to aluminum.

It is well established that aluminum (Al) is a neurotoxic agent that induces the production of free radicals in brain. Accumulation of free radicals may cause degenerative events of aging such as Alzheimers disease. On the other hand, melatonin (Mel) is a known antioxidant, which can directly act as free radical scavenger, or indirectly by inducing the expression of some genes linked to the antioxidant defense. In this study, AβPP female transgenic (Tg2576) (Tg) and wild‐type mice (5 months of age) were fed with Al lactate supplemented in the diet (1 mg Al/g diet). Simultaneously, animals received oral Mel (10 mg/kg) dissolved in tap water until the end of the study at 11 months of age. Four treatment groups were included for both Tg and wild‐type mice: control, Al only, Mel only, and Al+Mel. At the end of the period of treatment, hippocampus was removed and processed to examine the following oxidative stress markers: reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and thiobarbituric acid reactive substances (TBARS). Moreover, the gene expression of Cu‐ZnSOD, GR, and CAT was evaluated by real‐time RT‐PCR. Aluminum concentration in hippocampus was also determined. The biochemical changes observed in this tissue suggest that Al acts as a pro‐oxidant agent. Melatonin exerts an antioxidant action by increasing the mRNA levels of the antioxidant enzymes SOD, CAT, and GR evaluated in presence of Al and Mel, with independence of the animal model.

Aluminum exposure through the diet : Metal levels in AβPP transgenic mice, a model for Alzheimer's disease

Aluminum (Al), iron (Fe), copper (Cu), and zinc (Zn) cause have been implicated in the etiology of certain neurodegenerative disorders. Moreover, these elements cause the conformational changes of Alzheimers amyloid beta protein. In this study, we determined the concentrations of Al, Cu, Zn, Fe, and Mn in various tissues of Tg 2576 (AbetaPP transgenic) Al-treated mice. Female Tg 2576 mice and wild-type littermates were exposed through the diet to 1mg Al/g for 6 months. At 11 months of age, metal concentrations were measured in various tissues. In brain, Al levels were higher in hippocampus than in cortex and cerebellum. In hippocampus, Cu concentrations decreased in non-treated Tg 2576 mice, while Zn levels were higher in Al-treated mice. Copper, Zn, Mn and Fe concentrations in liver, kidney and bone were not affected by Al exposure. The current results show that Al exposure of Tg 2576 and wild-type mice did not produce important metal changes related with the genotype, responding similarly both groups of animals. As Tg 2576 mice have been considered as a potential model for Alzheimers disease (AD), the present results would not support the hypothetical role of Al in the etiology of AD.

Evaluation of the protective role of melatonin on the behavioral effects of aluminum in a mouse model of Alzheimer's disease.

In this study, five months old female transgenic (Tg2576) and wild-type mice were exposed for 6 months to aluminum (1mg Al/g diet), melatonin (10mg/kg/day), Al plus melatonin, or vehicle only (control group). General motor activity was evaluated using an open-field, whereas spatial learning and memory were assessed in a water maze. Aluminum levels in hippocampus, cortex and cerebellum were determined. Aluminum-treated Tg2576 mice showed higher Al levels in hippocampus than non-Al treated animals. No Al effects on general motor activity were found, while the open-field test showed an increased number of rearings in Tg2576 mice. A lower habituation pattern was observed in melatonin-treated animals. Differences in learning were noted in the water maze acquisition test, in which Al-treated Tg2576 mice showed more difficulties in learning the task than Al-exposed wild mice. No significant effects of melatonin in the acquisition task were observed. The present results indicate that Tg2576 mice are sensitive to high dietary Al levels. A significant protector role of melatonin on Al-induced behavioral effects was not observed.

Effects of oral exposure to silver nanoparticles on the sperm of rats

It has been demonstrated that exposure to silver nanoparticles (AgNPs) can induce toxicological effects in rodents. In this study, we investigated whether sub-chronic oral exposure to different doses of polyvinil pyrrolidone (PVP)-coated AgNPs (PVP-AgNPs) (50, 100 and 200mg/kg/day) could induce harmful effects on epididymal sperm rat parameters. Sperm motility, viability and morphology were examined. Moreover, a histological evaluation of testis and epididymis was also performed. High doses of PVP-AgNPs showed higher sperm morphology abnormalities, while a progressive, but not significant effect, was observed in other sperm parameters. The current results suggest that oral sub-chronic exposure to PVP-AgNPs induces slight toxicological effects in sperm rat parameters.

Oral exposure to silver nanoparticles increases oxidative stress markers in the liver of male rats and deregulates the insulin signalling pathway and p53 and cleaved caspase 3 protein expression

The present study was aimed at assessing the impact of AgNPs on the liver of male rats orally exposed to 0, 50, 100 and 200 mg/kg/day of polyvinyl pyrrolidone coated AgNPs (PVP-AgNPs) for 90 days. The induction of apoptotic cell death -by measuring the protein levels of the active form of caspase 3- and the levels of the microtubule-associated protein 1A/1B-light chain (LC3) protein were measured as a marker of the induction of autophagy. PVP-AgNPs caused an increase of the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver of male rats. However, the activity decreased after exposure to high amounts of PVP-AgNPs. Increased protein levels of IRS-1, AKT, GSK3β and mTOR proteins were observed in a dose-dependent manner. However, these proteins showed a decrease at 200 mg/kg/day. The same pattern was observed for the p53, p21 and cleaved caspase 3 protein levels. The current results suggest that the increase of ROS production by PVP-AgNPs stimulated SOD and CAT activity, as well as IRS-1, AKT, mTOR, p53, p21 and caspase 3 as protective mechanisms of cell survival and preserve DNA fidelity. However, cellular damage by excessive ROS production might induce the depletion of these survival mechanisms at 200 mg/kg/day.