Jordi Blanco

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.

Influencia de la medicina alternativa en el tratamiento antirretroviral de gran actividad

Objective: Over the last few years, there has been a notable increase in the use of alternative medicine by the general population. The aim of this study is two-fold. Firstly we will analyse the incidence of the use of medicinal plants in patients with HIV undergoing Highly Active Anti-Retroviral Therapy (HAART). Secondly, with the help of existing bibliographic information, we want to study the existence of possible interactions. Material and methods: We carried out a prospective study with a targeted interview (October to December 2007) on consenting patients with HIV undergoing HAART treatment. Results: Of the 193 patients that agreed to take part in the survey, 16.6 % confi rmed they used alternative medicinal therapies. In 46 % of the cases there was a potential interaction with the effectiveness of HAART. 46 % of the potential interactions were in the case of the patients who used grapefruit as an alternative medicine, 21 % in the case of patients using thistle and Echinacea respectively, 4 % for those using omega-3, Chinese herbs and ginseng. Conclusion: There is a signifi cant use of natural products by these groups of patients, of which a signifi cant percentage interact with HAART. A better understanding of the possible interactions with HAART and improved information offered to patients with HIV is needed.

The influence of alternative medicine in highly active antiretroviral treatment.

OBJECTIVE Over the last few years, there has been a notable increase in the use of alternative medicine by the general population. The aim of this study is two-fold. Firstly we will analyse the incidence of the use of medicinal plants in patients with HIV undergoing Highly Active Anti-Retroviral Therapy (HAART). Secondly, with the help of existing bibliographic information, we want to study the existence of possible interactions. MATERIAL AND METHODS We carried out a prospective study with a targeted interview (October to December 2007) on consenting patients with HIV undergoing HAART treatment. RESULTS Of the 193 patients that agreed to take part in the survey, 16.6 % confirmed they used alternative medicinal therapies. In 46 % of the cases there was a potential interaction with the effectiveness of HAART. 46 % of the potential interactions were in the case of the patients who used grapefruit as an alternative medicine, 21 % in the case of patients using thistle and Echinacea respectively, 4 % for those using omega-3, Chinese herbs and ginseng. CONCLUSION There is a significant use of natural products by these groups of patients, of which a significant percentage interact with HAART. A better understanding of the possible interactions with HAART and improved information offered to patients with HIV is needed.

Resveratrol Potently Counteracts Quercetin Starvation‐Induced Autophagy and Sensitizes HepG2 Cancer Cells to Apoptosis

SCOPE Resveratrol (RSV) has been described as a potent antioxidant, antisteatotic, and antitumor compound, and it has also been identified as a potent autophagy inducer. On the other hand, quercetin (QCT) is a dietary flavonoid with known antitumor, anti-inflammatory, and antidiabetic effects. Additionally, QCT increases autophagy. To study the hypothetical synergistic effect of both compounds, we test the combined effect of QCT and RSV on the autophagy process in HepG2 cells. METHODS AND RESULTS Autophagy is studied by western blotting, real-time RT-PCR, and cellular staining. Our results clearly indicate a bifunctional molecular effect of RSV. Both polyphenols are individually able to promote autophagy. Strikingly, when RSV is combined with QCT, it promotes a potent reduction of QCT-induced autophagy and influences proapoptotic signaling. CONCLUSION RSV acts differentially on the autophagic process depending on the cellular energetic state. We further characterize the molecular mechanisms related to this effect, and we observe that AMP-activated protein kinase (AMPK) phosphorylation, heme oxygenase 1 (HO-1) downregulation, lysosomal membrane permeabilization (LMP), and Zinc (Zn2+ ) dynamics could be important modulators of such RSV-related effects and could globally represent a promising strategy to sensitize cancer cells to QCT treatment.

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.

Anti-inflammatory and Proapoptotic Properties of the Natural Compound o-Orsellinaldehyde

Metabolic syndrome is a cluster of medical conditions that increases the risk of developing cardiovascular disease and type 2 diabetes. Numerous studies have shown that inflammation is directly involved in the onset of metabolic syndrome and related pathologies. In this study, in silico techniques were applied to a natural products database containing molecules isolated from mushrooms from the Catalan forests to predict molecules that can act as human nuclear-factor κβ kinase 2 (IKK-2) inhibitors. IKK-2 is the main component responsible for activating the nuclear-factor κβ transcription factor (NF-κβ). One of these predicted molecules was o-orsellinaldehyde, a molecule present in the mushroom Grifola frondosa. This study shows that o-orsellinaldehyde presents anti-inflammatory and pro-apoptotic properties by acting as IKK-2 inhibitor. Additionally, we suggest that the anti-inflammatory and pro-apoptotic properties of Grifola frondosa mushroom could partially be explained by the presence of o-orsellinaldehyde on its composition.

Postnatal exposure to chlorpyrifos produces long-term effects on spatial memory and the cholinergic system in mice in a sex- and APOE genotype-dependent manner

Organophosphorus pesticides - and in particular chlorpyrifos (CPF) - are extensively used worldwide. They mainly exert their toxicity by targeting the cholinergic system. Several studies suggested that the gene coding for apolipoprotein E (apoE), which is a risk factor for several diseases, can also confer different vulnerability to toxic insults. This study was aimed at assessing the long-term effects of postnatal exposure to CPF on learning and memory as well as the expression levels of several genes involved in cholinergic neurotransmission in mice. Both male and female apoE4-TR and C57BL/6 mice were exposed to either 0 or 1 mg/kg/day of CPF by oral gavage using a micropipette on postnatal days 10-15. At 9 months, they were tested in a Morris Water Maze (MWM) and the gene expression in the frontal cortex and hippocampus was evaluated. Our results show that, in males, CPF had an effect on the spatial retention, while in females, it altered the expression levels of nicotinic receptors. Furthermore, apoE4-TR mice performed the worst during the MWM retention and presented low expression levels in a considerable number of cholinergic genes. Taken together, the current results reveal long-term effects in mice nine months after postnatal exposure to CPF, which are modulated by sex and apoE4 genotype.

Mechanochemically synthesized Ag-based nanohybrids with unprecedented low toxicity in biomedical applications

&NA; A simple and innovative mechanochemical approach was employed to synthesize Ag‐polysaccharide nanohybrid materials that were proved to exhibit remarkable surface properties and structures for biomedical applications. The synthesized Ag nanomaterials possessed an unprecedented low cytotoxicity against human cell lines A549 and SH‐SY5Y as compared to similarly reported Ag nanomaterials due to the stability and low release of Ag+ and high biocompatibility of the nanohybrids. HighlightsAg‐polysaccharide nanohybrid are materials with high biocompatibility and extremely low cytotoxicity.The nanomaterials exhibited an unprecedented low cytotoxicity for human cell lines.The low cytotoxicity of the materials is essentially related to the fact that Ag‐PS nanohybrids release Ag+ very slowly into the solution.