Search

The conservation of seed germplasm is one of the most important ways to maintain the genetic variability of genetic resources, such as rice (Oryza sativa L.) and bean (Phaseolus vulgaris L.). These two species are fundamental for the food security and agribusiness of many countries, including Brazil. The efficient use of germplasm depends on the maintenance of the germination potential and the genetic integrity of conserved accessions. The objective of the present study was to analyze the genetic integrity of rice and bean accessions that have been maintained in long term conservation conditions. Six and four samples of two rice and bean accessions, respectively, were analyzed. Each sample was added to the collection in different years. First count, germination and germination speed index tests were carried out to evaluate the physiological quality of the seeds samples. Cytogenetic tests and comet assay were performed to evaluate the genetic integrity of the different samples. Significant differences were not observed among the samples of the two species in the cytogenetic tests. Eight of the 10 samples analyzed maintained high physiological quality after prolonged storage and presented acceptable levels of DNA damage (> 20%) in the comet assay. Evidences of DNA repair were detected in one sample. Data showed comet assay has potential to evaluate genetic integrity and DNA repair system in long term conserved seeds.

Microplastics in freshwater environments pose a serious threat to living beings. Polyethylene microplastics (PE-MP) are the type most used around the world as microbeads in personal care products, and they have been found in aquatic organisms. The behavior and toxicity of fluorescent PE-MP spheres with an average diameter of 58.9 μm were studied in adult, juvenile and embryo zebrafish (Danio rerio). The adults were studied for genotoxicity, cytotoxicity, histology and biochemical markers. Juveniles underwent a follow-up in the gastrointestinal (GI) tract with histologic observations, and embryos were studied for embryotoxicity with the FET-test. In adults, micronucleus test and comet assays found neither genotoxicity after acute exposure for 96 h at concentrations of 0.0, 12.5, 50 and 100 mg.L−1, nor cytotoxicity through the nuclear abnormalities test. Acetylcholinesterase (AChE), Glutathione-S-Transferase (GST) and Lactate Dehydrogenase (LDH) activities were measured in adults exposed for 96 h. The AChE and GST activities were significantly changed, while no changes occurred for LDH. In conclusion, these PE-MP spheres did not cause serious toxic effects in zebrafish because there was no internalization. The observed biochemical changes in AChE and GST may be associated with GI microbiological dysbiosis, previously reported. The PE-MP spheres in the intestine of juveniles remained present for 12–15 days on average after the post-exposure clearance study, showing a slow depuration. The histological analysis, in adults, found no internalization of these microbeads, with complete depuration. The PE-MP spheres did not cross the chorion barrier, showing no embryotoxic effects after exposures at 0.0, 6.25, 12.5, 50.0 or 100.0 mg.L−1 for 96 h.

Background Magnetic nanoparticles (MNPs) have been successfully tested for several purposes in medical applications. However, knowledge concerning the effects of nanostructures on elderly organisms is remarkably scarce. Purpose To fill part of this gap, this work aimed to investigate biocompatibility and bio-distribution aspects of magnetic nanoparticles coated with citrate (NpCit) in both elderly and young healthy mice. Methods NpCit (2.4 mg iron) was administered intraperitoneally, and its toxicity was evaluated for 28 days through clinical, biochemical, hematological, and histopathological examinations. In addition, its biodistribution was evaluated by spectrometric (inductively coupled plasma optical emission spectrometry) and histological methods. Results NpCit presented age-dependent effects, inducing very slight and temporary biochemical and hematological changes in young animals. These changes were even weaker than the effects of the aging process, especially those related to the hematological data, tumor necrosis factor alpha, and nitric oxide levels. On the other hand, NpCit showed a distinct set of results in the elderly group, sometimes reinforcing (decrease of lymphocytes and increase of monocytes) and sometimes opposing (erythrocyte parameters and cytokine levels) the aging changes. Leukocyte changes were still observed on the 28th day after treatment in the elderly group. Slight evidence of a decrease in liver and immune functions was detected in elderly mice treated or not treated with NpCit. It was noted that tissue damage or clinical changes related to aging or to the NpCit treatment were not observed. As detected for aging, the pattern of iron biodistribution was significantly different after NpCit administration: extra iron was detected until the 28th day, but in different organs of elderly (liver and kidneys) and young (spleen, liver, and lungs) mice. Conclusion Taken together, the data show NpCit to be a stable and reasonably biocompatible sample, especially for young mice, and thus appropriate for biomedical applications. The data showed important differences after NpCit treatment related to the animals' age, and this emphasizes the need for further studies in older animals to appropriately extend the benefits of nanotechnology to the elderly population.

Doxorubicin (DOX) is an anthracycline antibiotic used in the fight against many types of cancer. Although it is quite effective for this purpose, its clinical use is limited by its severe side effects, highlighting the relevance of efforts to identify substances that act to minimize these effects. In this work, we sought to verify the ability of andiroba oil (AO) and a nanoemulsion of andiroba oil (AN) to lessen the side effects of DOX. The animals were separated into 7 groups with 6 animals each: mice treated with AO (2000 mg/kg), AN (2000 mg/kg), the antineoplastic agent DOX (40 mg/kg), AO+DOX, AN+DOX and solvent controls was used of negative control (corn oil and nanoemulsion surfactant). AO and AN were administered for 14 consecutive days orally by gavage and on the 13th day, applied DOX by intraperitoneal route (i.p.), in order to evaluate the protective potential of andiroba. The animals were euthanized on the 15th day. Hematological, biochemical, histological, and immunohistochemical parameters were analyzed. Andiroba reduced several aspects of the severity of lesions caused by DOX, decreasing hematotoxicity and the severity of histological changes in the liver and kidneys, and reducing the frequency of apoptotic cell death. In many cases, AN showed greater efficacy than AO alone, reflecting the feasibility of using this nanotechnology to improve the pharmacokinetics of lipid compounds in the body. The study sheds new light on the therapeutic benefits of andiroba and suggests new ways for investigating how the quantity and quality of lipid compounds affect exposed organisms.

Psychiatric drugs are among the leading medications prescribed for humans, with their presence in aquatic environments raising concerns relating to potentially harmful effects on non-target organisms. Nortriptyline (NTP) is a selective serotonin-norepinephrine reuptake inhibitor antidepressant, widely used in clinics and found in environmental water matrices. In this study, we evaluated the toxic effects of NTP on zebrafish (Danio rerio) embryos and early larval stages. Developmental and mortality analyses were performed on zebrafish exposed to NTP for 168 h at concentrations ranging from 500 to 46,900 µg/L. Locomotor behaviour and acetylcholinesterase (AChE) activity were evaluated by exposing embryos/larvae to lower NTP concentrations (0.006–500 µg/L). The median lethal NTP concentration after 168 h exposure was 2190 µg/L. Although we did not identify significant developmental changes in the treated groups, lack of equilibrium was already visible in surviving larvae exposed to ≥ 500 µg/L NTP. The behavioural analyses showed that NTP was capable of modifying zebrafish larvae swimming behaviour, even at extremely low (0.006 and 0.088 µg/L) environmentally relevant concentrations. We consistently observed a significant reduction in AChE activity in the animals exposed to 500 µg/L NTP. Our results highlight acute toxic effects of NTP on the early-life stages of zebrafish. Most importantly, exposure to environmentally relevant NTP concentrations may affect zebrafish larvae locomotor behaviour, which in turn could reduce the fitness of the species. More studies involving chronic exposure and sensitive endpoints are warranted to better understand the effect of NTP in a more realistic exposure scenario.

Nanobiotechnology strategies for cancer treatments are currently being tested with increasing interest, except in elderly groups. It is well established that breast cancer incidence increases with age and that traditional therapies usually generate severe adverse effects, especially for elderly groups. To investigate if the benefits of nanotechnology could be extended to treating cancer in this group, citrate-coated maghemite nanoparticles (NpCit) were used for magnetohyperthermia (MHT) in combination with the administration of PLGA-Selol nanocapsule (NcSel), a formulation with antioxidant and antitumor activity. The combined therapies significantly inhibited breast Ehrlich tumor growth and prevented metastases to the lymph nodes, liver and lungs until 45 days after tumor induction, a better result than the group undergoing conventional drug treatment. The levels of TNF-α, associated with poor prognosis in Ehrlich tumor, were also normalized. Therefore, the results evidenced the potential use of these therapies for future clinical trials in elderly breast cancer patients.

Short time treatment with reduced dosages of selol-loaded PLGA nanocapsules (NcSel) combined with magnetic hyperthermia (MHT) is evaluated in aged Erhlich tumor-bearing mice. Clinical, hematological, biochemical, genotoxic and histopathological parameters are assessed during 7 d treatment with NcSel and MHT, separately or combined. The time evolution of the tumor volume is successfully modeled using the logistic mathematical model. The combined therapy comprising NcSel and MHT is able to hinder primary tumor growth and a case of complete tumor remission is recorded. Moreover, no metastasis was diagnosed and the adverse effects are negligible. NcSel plus MHT may represent an effective and safe alternative to cancer control in aged patients. Future clinical trials are encouraged.

The use of silver nanoparticles (AgNPs) result in an inevitable contact with aquatic environments. Here we study the behavior of AgNPs and the developmental toxicity in zebrafish embryos exposed to these nanoparticles (0-10 mg/L) with and without the presence of HA (20 mg/L), using zebrafish facility water (ZFW) and zebrafish growing media (ZGM). The presence of cations and HA gave rise to a decrease in Ag ion release and ζ-potential, an increase in the hydrodynamic diameter and oxidation of the AgNP surface. The results show that the presence of HA and cations in the media, as well as the silver speciation, i.e., the unusual presence of Ag3+, decreases the toxicity of AgNPs (LC50AgNPs: 1.19 mg/L; LC50AgNPs + HA: 3.56 mg/L), as well as silver bioavailability and toxicity in zebrafish embryos. Developmental alterations and the LC50 (1.19 mg/L) of AgNPs in ZFW were more relevant (p ≤ 0.05) than for AgNPs in ZGM (LC50 ˃ 10 mg/L). It was demonstrated that the bioaccumulation and toxicity of AgNPs depends on several factors including AgNPs concentration, nanoparticle aggregation, dissolved silver ions, speciation of silver ions, the amount of salt in the environment, the presence of humic substances and others, and different combinations of all of these factors.

Wildfire is very common in Brazilian savannas, and its effects on water, soil and aquatic/soil organisms are poorly understood. In this study, we observed the effects of fire, especially of ashes, on surface soil and subsurface water in a typical Brazilian savanna (Cerrado sensu strictu) for one year. Soil analyses (pH, organic matter content, potential acidity, K, Ca, Mg and P) and subsurface water analyses (NO3-, PO43- Mg2+, Ca2+ and K+) were assessed. We evaluated the ecotoxicological effects of ashes on three different endpoints and species, in fish Danio rerio (embryonic development), aquatic snail Biomphalaria glabrata (reproduction) and a soil species Enchytraeus sp. (reproduction). We found a higher amount of exchangeable cations and organic matter content in short-term fire effects on soil, but the higher availability of nutrients did not affect the soil pH in field plots. The effects of ashes on soil and subsurface water did not persist for one-year post-fire, except for organic matter content in burned areas. No toxic effects were observed on hatching success and incidences of developmental abnormalities in D. rerio embryos. However, ash input had adverse effects on reproduction in snails and enchytraeids. We reported a statistically significant decrease in snail eggs exposed to the 50g.L-1 and 100g.L-1 of ashes after four weeks (p

In the present study, graphitic carbon nitride (g-C3N4) was decorated with Fe3O4 nanoparticles by using an alternative, simple and environmentally friendly method of homogeneous precipitation with urea. The magnetic nanocomposite was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM-EDS), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), Brunauer–Emmett–Teller isotherms (BET), Zetametry, vibrating sample magnetometry, UV–vis absorption spectroscopy, and photoluminescence spectroscopy (PL). The acute toxicological effects of nanomaterials were evaluated in embryos/larvae of the zebrafish (Danio rerio). The performance of the nanocomposite for removal of methylene blue (MB), as a model pollutant, from water in different pH conditions was compared to that of pure g-C3N4 and a magnetic composite elaborated using conventional coprecipitation with NH4OH. The results showed that the nanocomposite synthesized with the new approach showed the best performance, corresponding to a removal rate of 98.3% in the alkaline medium. Regeneration studies showed that the proposed nanocomposite can be easily recovered by magnetic assistance and can be reused, keeping a good removal efficiency. The toxicological results showed that nanomaterials, pure and decorated, presented no acute toxicological effects in zebrafish at the concentrations recommended by OECD 236.

Loss of genetic integrity can occur during the long-term conservation of seeds. We have studied these effects in seeds of rice (Oryza sativa L.) and common bean (Phaseolus vulgaris L.) exposed to accelerated aging (elevated temperature and moisture) conditions. Tests of first count, germination, and germination speed index were performed to measure physiological quality; cytogenetic tests and comet assay were used to evaluate genetic integrity. With aging, we observed a decrease in mitotic index and an increase in the frequency of chromosomal alterations in root cells of imbibed seeds, as well as increased DNA damage (comet assay) in dry and imbibed seed embryos of both species. The comet assay can be a useful technique for measuring genetic integrity in seed conservation programs.

Nanoceria has a broad variety of industrial and pharmacological applications due to its antioxidant activity. Nanoceria can be modified by surface coating with polyelectrolyte brushes. Brushes can increase the surface charge of nanoceria, providing greater aqueous stability while reducing agglomeration. However, surface-coating also behaves as a barrier around nanoceria, affecting its redox equilibrium and, hence, its biological and toxicological properties. In the present study, we examined whether bare nanoceria (CeO2; 80–150 nm) and nanoceria modified by surface polymer brush, using negatively charged polyacrylic acid (CeO2@PAA) and positively charged poly (2-(methacryloyloxy)ethyl-trimethyl-ammonium chloride (CeO2@PMETAC), could induce systemic toxicity. As CeO2 has limited colloidal stability, which might result in vascular occlusion, intraperitoneal injection was used instead of intravenous administration. C57Bl/6 mice were four times injected with three different doses of each nanoceria-based sample (corresponding to 1.8, 5.3 and 16 mg Ce/kg BW/administration) for a total period of 14 days. CeO2@PMETAC induced a significant dose-dependent neutrophilia. Histopathological evaluation showed inflammatory processes in the capsule of liver, kidney, and spleen of animals at all doses of CeO2@PMETAC, and with the highest dose of CeO2@PAA and CeO2. However, none of the nanoceria-based samples tested increased the level of DNA damage or micronuclei in blood cells, even though Ce was detected by inductively coupled plasma mass spectrometry analyses in the bone marrow. Only CeO2@PMETAC induced the presence of megakaryocytes in the spleen. A higher accumulation of Ce in mononuclear phagocyte system organs (liver, spleen and bone marrow) was observed after CeO2@PMETAC treatment compared with CeO2@PAA and CeO2.

This study aimed to assess the feasibility of comet and cytogenetic tests as tools for evaluating genomic instability in seeds of Oryza sativa L. (rice) and Phaseolus vulgaris (beans) L. from gene banks. Rice and beans were exposed to methyl methanesulfonate (MMS) as a reference DNA damaging agent. Seeds of two accessions of rice and beans were obtained from Embrapa Rice and Beans - Brazil. Seed groups were imbibed in three concentrations of MMS for three periods of time to carry out cytogenetic tests, and for one period for the comet test. At concentrations of 10 and 15 mg/L, MMS induced cytotoxic and/or mutagenic effects in the meristematic cells of roots from all the accessions of both species. In the comet test, MMS induced genotoxic effects at all the concentrations in the evaluated accessions of rice and beans, except in one accession of beans at the lowest concentration (5 mg/L). Both species showed sensitivity to MMS. The comet test can be proposed for the measurement of genomic instability in accessions of rice and beans in gene banks, as being more sensitive than the cytogenetic tests used.

The Carapa guianensis (andiroba) oil is commonly used by the Amazon population for medicinal purposes. The objective of this study was to determine the genotoxic and antigenotoxic potential of the andiroba oil (AO) and nanoemulsion (AN) using Swiss mice. Therefore, we used the comet assay and micronucleus test. The AO predominant compounds were oleic (39.13%), palmitic (33.22%), and linoleic (16.86%) acids. AN composition obeyed the surfactant/oil ratio of 0.69, and the Tween 80/Span 80 ratio was held at 0.9. Our results showed no cytotoxicity or genotoxicity in the mice treated with AO and AN alone. However, there was a significant reduction in the polychromatic erythrocytes (PCEs) numbers in all groups treated with doxorubicin (DOX), including those pretreated with AO and AN. Thus, the samples tested did not protect against DOX. On the other hand, our results showed a large increase in micronucleus (MN) formation when the mice were treated with DOX alone; these numbers were reduced when the animals were pretreated with AO and AN. The results indicate a protective effect of andiroba on MN formation and show no evidence of genotoxicity in mice.

The use of silver nanoparticles (AgNPs) result in an inevitable contact with aquatic environments. Here we study the behavior of AgNPs and the developmental toxicity in zebrafish embryos exposed to these nanoparticles (0-10 mg/L) with and without the presence of HA (20 mg/L), using zebrafish facility water (ZFW) and zebrafish growing media (ZGM). The presence of cations and HA gave rise to a decrease in Ag ion release and ζ-potential, an increase in the hydrodynamic diameter and oxidation of the AgNP surface. The results show that the presence of HA and cations in the media, as well as the silver speciation, i.e., the unusual presence of Ag

In recent years silver nanoparticles (AgNPs) have found their way into the consumer market as part of textiles, coating and devices. The disposal of products containing AgNPs can lead to NP accumulation in aquatic environments and to the formation of sediments by adsorption with humic acid (HA). Toxicological end points of AgNPs in the presence of HA were assessed in adult zebrafish. Zebrafish (n = 7/group) were exposed for 96 h to 0, 10, 20, 30, 40 and 60 mg/L AgNPs with or without 20 mg/L HA. The toxicity of AgNPs+HA was lower (LC50 = 40.56 mg/L) than for AgNPs (LC50 = 25.0 mg/L). AgNPs+HA did not induce significant changes on DNA fragmentation and organ histology. The amount of silver per organ were mesured by μPIXE and ICP-MS. TEM and DLS analysis showed that though there is complexation between HA and AgNPs, μPIXE shows that the biological fate of AgNPs was not altered by HA. However, silver concentration was higher in fish exposed to AgNPs than to AgNPs+HA. These results show that HA influence the behavior, bioavailability, and toxicity of AgNPs in zebrafish reducing silver uptake and fish mortality.

Bioinsecticides from Bacillus thuringiensis (Bt) are widely used around the world in biological control against larval stages of many insect species. Bt has been considered a biopesticide that is highly specific to different orders of insects, non-polluting and harmless to humans and other vertebrates, thus becoming a viable alternative for combating agricultural pests and insect vectors of diseases. The family of Bt δ-endotoxins are crystal-protein inclusions showing toxicity to insects’ midgut, causing cell lysis leading to starvation, septicemia and death. The aim of this study is to evaluate the genotoxic potential of recombinant Bt spore–crystals expressing Cry1Ia, Cry10Aa and Cry1Ba6 on peripheral erythrocyte cells of Oreochromis niloticus, through comet assay, micronucleus (MN) test and nuclear abnormalities (NA) analysis. Fish (n = 10/group) were exposed for 96 h at 107 spores 30 l−1, 108 spores 30 l−1 or 109 spores 30 l−1 of Bt spore–crystals. Cry1Ia showed a significant increase in comet cells at levels 1 and 2, but not at levels 3 and 4, so it was not mutagenic nor did it induce MN or NA. These three spore–crystals showed some fish toxicity at only the highest exposure level, which normally does not occur in the field.

Andiroba oil (AO) is obtained from an Amazonian plant and is used in traditional medicine. We carried out a comparative study to test the cytotoxicity, genotoxicity, and hematotoxicity of the oil and its nanoemulsion (AN) in vitro (fibroblasts, lineage NIH/3T3) and in vivo (Swiss mice). The AN was characterized by DLS/Zeta, and its stability was investigated for 120 days. The biological activity of AN was assessed in vitro by MTT test and cell morphology analyses and in vivo by micronucleus, comet, and hematotoxicity tests. The AN presented a hydrodynamic diameter (Hd) of 142.5±3.0 and PDI of 0.272±0.007 and good stability at room temperature. The MTT test evidenced the cytotoxicity of AO and of AN only at their highest concentrations, but AN showed lower cytotoxicity than AO. A lower cytotoxicity of AN, when compared to AO, is in fact an interesting data suggesting that during therapeutic application there will be a lower impact in the cell viability of healthy cells. Cytotoxicity, genotoxicity, and hematotoxicity were not observed in vivo. These tests on the biological and toxicological effects of andiroba oil and nanostructured oil are still initial ones but will give a direction to future application in cosmetics and/or the development of new phytotherapics.

Melanoma is the most aggressive and lethal form of skin cancer, responsible for >80% of deaths. Standard treatments for late-stage melanoma usually present poor results, leading to life-threatening side effects and low overall survival. Thus, it is necessary to rethink treatment strategies and design new tools for the treatment of this disease. On that ground, we hereby report the use of acai oil in nanoemulsion (NanoA) as a novel photosensitizer for photodynamic therapy (PDT) used to treat melanoma in in vitro and in vivo experimental models. NIH/3T3 normal cells and B16F10 melanoma cell lines were treated with PDT and presented 85% cell death for melanoma cells, while maintaining high viability in normal cells. Flow cytometry indicated that cell death occurred by late apoptosis/necrosis. Tumor bearing C57BL/6 mice treated five times with PDT using acai oil in nanoemulsion showed tumor volume reduction of 82% in comparison to control/tumor group. Necrotic tissue per tumor area reached its highest value in PDT-treated mice, supporting PDT efficacy. Overall, acai oil in nanoemulsion was an effective photosensitizer, representing a promising source of new photosensitizing molecules for PDT treatment of melanoma, a tumor with an inherent tendency to be refractory for this type of therapy.

Andirobeira is an Amazonian tree, the seeds of which produce a commercially valuable oil that is used in folk medicine and in the cosmetic industry. Andiroba oil contains components with anti-inflammatory, cicatrizing and insect-repellant actions. However, virtually nothing is known of the safety of this oil for humans. The aim of this work was therefore to investigate the hematotoxicity, genotoxicity and mutagenicity of andiroba oil using the comet and micronucleus assays, and to assess its antioxidant properties and lipidome as a means of addressing safety issues. For the experiments, andiroba oil was administered by gavage for 14 consecutive days in nulliparous female Swiss mice randomly distributed in four groups: negative control and three doses of oil (500, 1000 and 2000 mg/kg/day). These doses were chosen based on recommendations of the OECD guideline no. 474 (1997). GC/MS was used to investigate the free fatty acid, cholesterol and triterpene content of andiroba oil in a lipidomic analysis. No clinical or behavioral alterations were observed throughout the period of treatment, and exposure to andiroba oil at the doses and conditions used here did not result in hematotoxic, genotoxic or mutagenic effects. Tests in vitro showed that oil sample 3 from southwestern of Brazilian Amazon had a high antioxidant capacity that may protect biological systems from oxidative stress, although this activity remains to be demonstrated in vivo.

Magnetic exfoliated vermiculite is a synthetic nanocomposite that quickly and efficiently absorbs organic compounds such as oil from water bodies. It was developed primarily to mitigate pollution, but the possible adverse impacts of its application have not yet been evaluated. In this context, the acute toxicity of magnetic exfoliated vermiculite and exfoliated vermiculite was herein assessed by genotoxic and histopathological biomarkers in zebrafish (Danio rerio). DNA fragmentation was statistically significant for all groups exposed to the magnetic exfoliated vermiculite and for fish exposed to the highest concentration (200mg/L) of exfoliated vermiculite, whereas the micronucleus frequency, nuclear abnormalities and histopathological alterations were not statistically significant for the fish exposed to these materials. In the intestinal lumen, epithelial cells and goblet cells, we found the presence of magnetic exfoliated vermiculite and exfoliated vermiculite, but no alterations or presence of the materials-test in the gills or liver were observed. Our findings suggest that the use of magnetic exfoliated vermiculite and exfoliated vermiculite during standard ecotoxicological assays caused DNA damage in D. rerio, whose alterations may be likely to be repaired, indicating that the magnetic nanoparticles have the ability to promote genotoxic damage, such as DNA fragmentation, but not mutagenic effects.

Accepted Manuscript.-- et al., Hematotoxicity of magnetite nanoparticles coated with dimercaptosuccinic acid (DMSA) and polyethylene glycol (PEG) has been evaluated by determining their safety in vitro and in vivo in a rat model up to 30 days after administration of a single dose. The in vitro analysis consists of global plasma coagulation (PT, aPTT, and fibrinogen) and platelet aggregation tests while the hematotoxicity studies in vivo include a complete blood count and the possible genotoxic effect analysis in the bone marrow hematopoietic function. Prolonged aPTT values indicate a higher anticoagulant effect for NP-DMSA compared with PEG-coated nanoparticles as a consequence of the higher surface charge of the former. The in vivo tests showed that these bioferrofluids do not cause genotoxic effects, affect erythropoiesis or increase the number of immature erythrocytes in the bone marrow at the analyzed dose. However, nanoparticle administration showed a significant effect on the leukocyte counts in animals treated with DMSA coated nanoparticles 24 h after injection. This response is not observed in animals treated with PEG modified nanoparticles which justifies the use of this polymer in biomasking strategies., L.M.A.A. acknowledges financial support from the Spanish Ministry of Science and Innovation FPI research grants. Technical support from the University Hospital Lozano Blesa, Zaragoza, Spain and from María Angeles Gracia, Ana Isabel Martínez de Ternero, Maria Rosa Borrell Sanz. AR holds a predoctoral fellowship from a CSIC-CITMA collaborative project (B01CU2009; ICMM, 2011–2014) and a short-term fellowship from CNPq (DTI-2; 383934/2013-3). This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (MAT2011-23641 and MAT2011-25991).

Long-term in vivo studies in murine models have shown that DMSA-coated nanoparticles accumulate in spleen, liver and lung tissues during extended periods of time (at least up to 3 months) without any significant signs of toxicity detected. During that time, nanoparticles undergo a process of biotransformation either by reducing the size or the particle aggregation or both. Using a rat model, we have evaluated the transformations of magnetic nanoparticles injected at low doses. Particles with two different coatings, dimercaptosuccinic acid (NP-DMSA) and polyethylene glycol (NP-PEG-(NH2)2) have been administered to animals, to evaluate the role of coating in the degradation of the particles. We have found that low doses of magnetic nanoparticles are quickly metabolized by the animals. In fact, using a nanoparticle dose four times lower than in previous experiments, NP-DMSA were not observed 24 h after the administration either in the liver or in the lungs. Interestingly, an increased amount of ferritin, the iron storage protein, was observed in liver tissues from rats that were treated with the low dose of NP-DMSA in comparison with the control ones, suggesting a rapid metabolization of the particles into ferritin iron. On the other side we have found that, NP-PEG-(NH2)2 are still detectable in several organs 24 h after their administration at low doses. Probably, due to the longer circulation times of the NP-PEG-(NH2)2, there is a delay in the arrival of the particles to the tissue and this is the reason why we are able to see the particles 24 h post-administration. PEG coating could also be protecting the nanoparticles from rapid degradation of the reticuloendothelial system. Knowledge on the biodistribution, circulation time and degradation processes is required to gain a better understanding of the safety evaluation of this kind of nanomaterial for biomedical applications., Amalia Ruiz holds a predoctoral fellowship from a CSIC-CITMA collaborative project (B01CU2009; ICMM, 2011–2014) and a short-term fellowship from CNPq (DTI-2; 383934/2013-3). Lucía Gutiérrez is the beneficiary of a post-doctoral grant from the AXA Research Fund. This work was partially supported by the European Commission (MULTIFUN, no. 262943).

Itraconazol, um antifúngico de amplo espectro, possui muitos efeitos colaterais e o uso de nanossistemas para a entrega de fármacos tem sido proposto como um método para otimizar a farmacocinética da droga e reduzir os efeitos colaterais. Um procedimento de cromatografia líquida de alta performance (HPLC) utilizando detecção fluorimétrica foi desenvolvido para a determinação de itraconazol em nanopartículas do copolímero de ácido láctico e glicólico, plasma e tecidos. A linearidade, limites de detecção e quantificação, recuperação, precisão, seletividade e estabilidade do método foram estabelecidas. O método desenvolvido foi testado na detecção e quantificação de itraconazol na biodistribuição de nanopartículas administrados intraperitonealmente em camundongos fêmeas Balb/C. Neste estudo foi desenvolvido um método analítico de HPLC com detecção fluorimétrica para quantificação de itraconazole em nanopartículas poliméricas, tecidos e plasma, sendo ele sensível, de baixo custo, viável para uso de rotina e com potencial para aplicação na biodistribuição e estudos farmacocinéticos de itraconazole em nanossistemas. Itraconazole, a broad-spectrum anti-fungal, has many side effects, and nanosystems for drug delivery have been proposed as a method to optimize the drug's pharmacokinetics and reduce side effects. An high performance liquid chromatography (HPLC) procedure using fluorometric detection was developed for determination of itraconazole in polymeric poly(lactic-co-glycolic acid) nanoparticles, plasma and tissue. Linearity, limits of detection and quantification, recovery, precision, selectivity and stability were established. The developed method was tested in itraconazole detection and quantification of biodistribution of nanoparticles administered intraperitoneally to Balb/C female mice. This study developed an analytical method for HPLC with fluorometric detection for quantification of itraconazole in polymeric nanoparticles, tissue and plasma, which is sensitive, low cost, viable for routine usage and with potential for application in itraconazole biodistribution and pharmacokinetics studies.

Iron oxides that exhibit magnetic properties have been widely studied not only from an academic standpoint, but also for numerous applications in different fields of knowledge, such as biomedical and technological research. In this work, magnetite and maghemite nanoparticles were synthesized by chemical coprecipitation of FeCl2·4H2O and FeCl3·6H2O (proportion of 1 : 2) in three different cases using two bases (sodium hydroxide and hydroxide ammonium) as precipitants. The chemical coprecipitation method was selected for its simplicity, convenience, reproducibility, and low cost in the use of glassware. The nanostructured materials were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD) and magnetometry (VSM). The objective of this work is to study the variation in the morphological characteristics and physical properties of nanoparticles magnetic as a function of the different production processes. As observed by TEM, the materials obtained from the precipitating agent NH4OH are more uniform than those obtained with NaOH. From XRD pattern analysis, it appears that the obtained materials correspond to magnetite and maghemite and, from magnetometry VSM analysis, show high magnetization as a function of the magnetic field at room temperature, indicating that these materials are superparamagnetic.

O óleo-resina de copaíba obtido do gênero Copaifera L., Fabaceae, é largamente utilizado na medicina popular como antiinflamatório, antimicrobiano e antitumoral. Porém, informações sobre seu potencial tóxico são escassos na literatura. O objetivo deste estudo foi estabelecer a toxicidade oral aguda e os possíveis efeitos neurotóxicos relacionados à ingestão do óleo-resina de Copaifera reticulata Ducke, Fabaceae, em ratas Wistar. O estudo foi conduzido com quinze ratas nulíparas distribuídas nos grupos de doses 300 e 2000 mg/kg pc de óleo-resina administrado por gavagem. Os resultados obtidos mostraram que nestas doses não houve sinais clínicos de toxicidade ou neurotoxicidade, alteração no consumo de ração ou alteração no peso corpóreo. A dose letal aguda foi estimada como maior que 2000 mg/kg pc e classificada como categoria 5, segundo o Guia OECD 423. Estes resultados indicam que existe uma relativa margem de segurança para o uso do óleo-resina de copaíba como agente terapêutico, embora estudos toxicológicos adicionais sejam ainda necessários, principalmente com a administração repetida de baixas doses. Copaiba oil-resin obtained from Copaifera L. genus, Fabaceae, is largely used in popular medicine as antinflammatory, antimicrobial and antitumoral. Information concerning the potential toxicity of this oil is limited in the literature. The goal of this study was to investigate the acute toxicity and the possible neurotoxic effects related to the ingestion of Copaifera reticulata Ducke, Fabaceae, oil-resin using female Wistar rats. Fifteen nulliparous rats were used and distributed in the experimental groups orally exposed to doses of 300 e 2000 mg/kg bw of oil-resin (gavage). No overt clinical signs of toxicity or neurotoxicity, alteration of food consumption or body weight were observed in the animals at the tested doses. The lethal oral toxicity was estimated to be higher than 2000 mg/kg bw, classified as category 5 according to OECD Guide 423. These results indicate that there is a certain safety margin associated with the use of copaiba as therapeutic agent, although additional toxicological studies are still necessary, mainly using repeated low doses.