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1.
Environ Res ; 234: 116030, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37142080

RESUMO

Intensification of crop cultivation can have detrimental environmental consequences that however can be prevented by monitoring of the specific biological indicators sensitive to changes in the ambient environment. In this study the impact of crop type (spring wheat and corn) and cultivation intensity on the community of ground beetles (Coleoptera: Carabidae) in the forest-steppe of Western Siberia was investigated. A total of 39 species from 15 genera were collected. Ground beetles' community was characterized by a high evenness of species distribution across the agroecosystems. The average Jaccard's similarity index for species presence/absence was 65%, and for abundance it was 54%. The significant difference in the distribution of predatory and mixophytophages ground beetles in wheat crops (U test, P < 0.05) can be justified by the constant suppression of the weed component and the use of insecticides that lead to the dominance of the predators. Fauna of wheat crops was more diverse than that in corn (Margalef index, U test, P < 0.05). No significant differences in biological diversity indexes, except for the Simpson dominance index (U test, P < 0.05, wheat), were found in ground beetle communities in crops at different levels of intensification. A certain differentiation of predatory species was caused by the selective occurrence of the litter-soil species, especially abundant in the row-crop. The specificity of the ground beetle community of corn crops may have been caused by repeated inter-row tillage, which influenced the increase in porosity and topsoil relief and contributed to the creation of favorable microclimatic conditions. In general, the applied level of agrotechnological intensification had no significant effect on the species composition and ecological structure of beetle communities in agrolandscapes. The use of bioindicators made it possible to assess the environmental sustainability of the agricultural environment and also creates the prerequisites for the development of ecologically directed correction of agrotechnological operations in agroecosystem management.


Assuntos
Besouros , Ecossistema , Animais , Biomarcadores Ambientais , Biodiversidade , Solo , Triticum , Zea mays , Produtos Agrícolas
2.
Bull Exp Biol Med ; 174(3): 365-369, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36729327

RESUMO

Liver morphology, intensity of apoptosis, and activity of xenobiotic metabolism enzymes were studied in a chronic model experiment in rats receiving a mixture of 6 pesticides against the background of life-long diets with adequate and insufficient supply of water-soluble vitamins. The dose of each pesticide in the mixture did not exceed the acceptable daily intake (1 ADI). It was found that chronic exposure to low doses of anthropogenic toxicants in combination with permanent vitamin deficiency provokes a number of liver changes, such as increased apoptosis activity, cytochrome P450 system depletion, steatosis, and inflammatory infiltration, which is a potential health risk factor.


Assuntos
Deficiência de Vitaminas , Fígado , Ratos , Animais , Fígado/metabolismo , Deficiência de Vitaminas/metabolismo , Vitaminas , Sistema Enzimático do Citocromo P-450/metabolismo , Biomarcadores/metabolismo
3.
Nanotoxicology ; 15(7): 973-994, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34213984

RESUMO

Colorectal cancer (CRC), is the second cause of cancer-related deaths worldwide is one of the most prevalent types of cancers. Conventional treatment continues to rely on surgery, chemotherapy, and radiotherapy, but for advanced cases, adjuvant chemotherapy remains the main approach for improving surgical outcomes and lower the disease recurrence probability. Chemotherapy-induced gastrointestinal (GI) toxicity is the main dose-limiting factor for many chemotherapeutic regimens, including 5-FU, and one of the biggest oncological challenges. Up to 40% of the patients receiving 5-FU get mucositis, 10-15% of which develop severe symptoms. In this context, our study aimed to develop a bioinspired nanosized drug delivery system as a strategy to reduce 5-FU associated side effects, such as GI mucositis. To this end, SF-based nanoparticles were prepared and characterized in terms of size and morphology, as well as in terms of in vitro antitumoral activity on a biomimetic colorectal cancer model by investigation of apoptosis, DNA fragmentation, and release of reactive oxygen species. Additionally, the capacity of the SF-based nanocarriers to offer intestinal protection against 5-FU-induced GI mucositis was evaluated in vivo using a mouse model that mimics the chemotherapy-associated gut mucositis occurring in colorectal cancer. Our studies show that silk fibroin nanoparticles efficiently deliver 5-FU to tumor cells in vitro while protecting against drug-induced GI mucositis in a mouse model.


Assuntos
Neoplasias Colorretais , Fibroínas , Mucosite , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/toxicidade , Células HT29 , Humanos
4.
Toxicol Rep ; 8: 1207-1219, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34189057

RESUMO

Coal dust is a source of pollution not only for atmospheric air but also for the marine environment. In places of storage and handling of coal near water bodies, visible pollution of the water area can be observed. Coal, despite its natural origin, can be referred to as anthropogenic sources of pollution. If coal microparticles enter the marine environment, it may cause both physical and toxic effects on organisms. The purpose of this review is to assess the stage of knowledge of the impact of coal particles on marine organisms, to identify the main factors affecting them, and to define advanced research directions. The results presented in the review have shown that coal dust in seawater is generally not an inert substance for marine organisms, and there is a need for further study of the impact of coal dust particles on marine ecosystems.

5.
Food Chem Toxicol ; 133: 110748, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31377140

RESUMO

Hexavalent chromium raises high concern because of its wide industrial applications and reported toxicity. Long-term (135 days) oral exposure of Wistar rats to chromium in the form of K2Cr2O7 (exposed group~20 mg/kg/day) led to a decrease in thymus mass and thymocytes' number and caused structural and functional changes in the lymph nodes and spleen, namely lymphoreticular hyperplasia and plasmocytic macrophage transformation. Programmed cell death was increased in both thymocytes and splenocytes and decreased in lymphocytes in the T-zones of spleen and lymph nodes. Moreover, Cr (VI) administration decreased myeloid cells' and neutrophils' number, while it increased lymphoid and erythroid cells' number in bone marrow. Cr (VI) immune system effects seem to be related to oxidative stress induction, as depicted by the increased levels of diene conjugates and malondialdehyde in the spleen and liver and by the decreased activity of catalase and superoxide dismutase in rats' erythrocytes. In addition, exposure to Cr (VI) decreased copper, nickel and iron concentrations in blood and liver, while Cr levels in blood, spleen and liver were increased, as expected. The observed changes in the series of immunological parameters studied contribute to the development of new approaches for the prevention of low level Cr exposure toxicity.


Assuntos
Cromo/toxicidade , Linfonodos/efeitos dos fármacos , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Imuno-Histoquímica , Linfonodos/metabolismo , Contagem de Linfócitos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Baço/metabolismo , Linfócitos T/metabolismo , Timócitos/metabolismo , Timo/metabolismo , Timo/patologia
6.
Food Chem Toxicol ; 127: 42-52, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30836108

RESUMO

This study focused on defining the in vitro behavior of amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles toward whole blood, blood plasma and blood cells in order to assess nanoparticle blood compatibility. In addition, possible effects on endothelium cell growth/viability were evaluated. The Amph-PVP nanoparticles were formed via self-assembling in aqueous media and composed of a hydrophobic alkyl core and a hydrophilic PVP outer shell. Their blood compatibility was evaluated by investigating their effect on red blood cells (RBCs) or erythrocytes, white blood cells (WBCs) or leukocytes, platelets (PLTs) and on complement system activation. Our results clearly demonstrate that the Amph-PVP nanoparticles are stable in presence of blood serum, have no significant effects on the function of RBCs, WBCs, PLTs and complement system activation. The Amph-PVP nanoparticles did not show considerable hemolytic or inflammatory effect, neither influence on platelet aggregation, coagulation process, or complement activation at the tested concentration range of 0.05-0.5 mg/ml. The Amph-PVP nanoparticles did not exhibit any significant effect on HMEC-1 microvascular skin endothelial cells' growth in in vitro experiments. The excellent blood compatibility of the Amph-PVP nanoparticles and the lack of effect on endothelium cell growth/viability represent a crucial feature dictating their further study as novel drug delivery systems.


Assuntos
Materiais Biocompatíveis , Plaquetas/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Nanopartículas/toxicidade , Pirrolidinonas/toxicidade , Linhagem Celular , Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Humanos , Técnicas In Vitro , Nanopartículas/química , Pirrolidinonas/química , Pele/irrigação sanguínea , Pele/citologia
7.
Toxicol Rep ; 6: 111-117, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30622905

RESUMO

The world biodiesel production is increasing at a rapid rate. Despite its perceived safety for the environment, more detailed toxicity studies are mandatory, especially in the field of aquatic toxicology. While considerable attention has been paid to biodiesel combustion emissions, the toxicity of biodiesel in the aquatic environment has been poorly understood. In our study, we used an algae culture growth-inhibition test (OECD 201) for the comparison of the toxicity of B100 (pure biodiesel), produced by methanol transesterification of waste cooking oil (yellow grease), B0 (petroleum diesel fuel) and B20 (diesel-biodiesel blended of 20% biodiesel and 80% petroleum diesel fuel by volume). Two marine diatoms Attheya ussuriensis and Chaetoceros muelleri, the red algae Porphyridium purpureum and Raphidophyte Heterosigma akashiwo were employed as the aquatic test organisms. A sample of biodiesel from waste cooking oil without dilution with petroleum diesel (B100) showed the highest level of toxicity for the microalgae A. ussuriensis, C. muelleri and H. akashiwo, compared to hexane, methanol, petroleum diesel (B0) and diluted sample (B20). The acute EC50 in the growth-inhibition test (96 h exposure) of B100 for the four species was in the range of 3.75-23.95 g/L whereas the chronic toxicity EC50 (7d exposure) was in the range of 0.42-16.09 g/L.

8.
Toxicol Rep ; 6: 120-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30671347

RESUMO

This research article investigates the particulate matter originated from the exhaust emissions of 20 bus models, within the territory of Vladivostok, Russian Federation. The majority of evaluated buses (17 out of 20) had emissions of large particles with sizes greater than 400 µm, which account for more than 80% of all measured particles. The analysis of the elemental composition showed that the exhaust emissions contained Al, Cd, Cu, Fe, Mg, Ni, Pb, and Zn, with the concentration of Zn prevailing in all samples by two to three orders of magnitude higher than the concentrations of the other elements.

9.
Hum Exp Toxicol ; 38(1): 148-154, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29998771

RESUMO

Carbon monoxide (CO) poisoning is a significant cause of death especially in developing countries. The current study investigated cardioprotective effects of insulin in CO-poisoned rats. Male rats were exposed to 3000 ppm CO for 1 h. Insulin (100 and 120 U/kg intraperitoneally) was immediately administered after CO exposure and on the next 4 days, on a daily basis (a total of 5 doses). On day 5, animals were euthanized, and the hearts were harvested for Western blotting and histopathological studies. The electrocardiograms (ECG) were recorded postexposure to CO and after the completion of insulin treatment period. Histopathological evaluations showed reduction of myocardial necrosis in insulin-treated animals compared to controls. BAX/BCL2 ratio, as a proapoptotic index, was significantly reduced in treatment groups ( p < 0.01). The ECG findings showed no differences among groups; also, compared to control animals, myocardial Akt levels were not markedly affected by insulin. The current study showed that insulin significantly reduces myocardial necrotic and apoptotic indices in CO-poisoned rats.


Assuntos
Intoxicação por Monóxido de Carbono/tratamento farmacológico , Cardiotônicos/uso terapêutico , Insulina/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Intoxicação por Monóxido de Carbono/metabolismo , Intoxicação por Monóxido de Carbono/patologia , Intoxicação por Monóxido de Carbono/fisiopatologia , Carboxihemoglobina/análise , Eletrocardiografia , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar
10.
Sci Rep ; 8(1): 17169, 2018 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-30464198

RESUMO

Arc welding operations are considered to be risky procedures by generating hazardous welding fume for human health. This study focuses on the key characteristics, as well as dispersion models, of welding fumes within a work zone. Commercial and widely used types of electrodes with various types of covering (rutile, basic, acidic and rutile-cellulose) were used in a series of experiments on arc welding operations, under 100 and 150 amps of electric current. According to the results of this study, maximum levels of pollution with particles of PM10 fraction occur in the workspace during arc welding operations. Disregarding the types of electrodes used, the 3D models of dispersion of the РМ10 particles at the floor plane exhibit corrugated morphologies while also demonstrate high concentrations of the РМ10 particles at distances 0-3 m and 4-5 m from the emission source. The morphology of these particles is represented by solid and hollow spheres, 'nucleus-shell' structures, perforated spheres, sharp-edged plates, agglomerates of the tree-like (coral) shape. At last the bifractional mechanism of fume particle formation for this type of electrodes is also shown and described. In this article results are reported, which demonstrate the hazards of the arc welding process for human health. The results of the characterization of WFs reported improve our understanding of risks that these operations pose to human health and may strengthen the need for their control and mitigation.


Assuntos
Poluentes Atmosféricos/análise , Eletrodos , Material Particulado/análise , Fumaça , Soldagem/métodos , Humanos
11.
Toxicol Rep ; 5: 1107-1113, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30450285

RESUMO

Since ancient times the concept of dose response, from a toxicological perspective, has been a matter of concern. Already by the 8th century BC and over the years, many enlightened people have attempted to interpret this phenomenon, observing and coming across its results and practical implementation through exposure to chemical substances, either from natural or synthetic sources. Nowadays, the environmental exposure of human populations to chemicals in terms of quantity and quality might differ. Nevertheless, dose response still remains an issue joining hands with scientific and technological progress. The aim of the present review is not only to briefly recount the history of the dose response concept, from ancient time theories to novel approaches, but also to draw the outline of challenges and requirements toxicology science needs to fulfill.

12.
Toxicology ; 406-407: 129-136, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30063941

RESUMO

Organophosphates are a large class of chemicals, initially invented in 1850 and since then they have been applied in numerous aspects of science to serve our purposes. Their mechanism of action in living organisms involves the irreversible inhibition of acetylcholinesterase, therefore they interfere with neuromuscular signal transmission. Due to the systematic and exaggerated use of these chemicals, there is massive exposure to them, hence there is great concern regarding the ramifications to all mammalian organisms. It has been widely accepted that over-exposure to organophosphates, has a deleterious impact on the renal tissue and subsequently on the renal function. Despite the significance of this global issue, limited knowledge exists, regarding the effect of these substances on our health. Therefore, new and extensive research is required to expand our knowledge and ensure proper guidance regarding the use of organophosphates as well the protection against their detrimental consequences. The aim of this review is to negotiate the effect of organophosphate exposure on renal tissue and kidney function.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Inibidores da Colinesterase/toxicidade , Inseticidas/toxicidade , Organofosfatos/toxicidade , Injúria Renal Aguda/metabolismo , Animais , Inibidores da Colinesterase/metabolismo , Humanos , Inseticidas/metabolismo , Organofosfatos/metabolismo
13.
Toxicology ; 409: 137-143, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30055296

RESUMO

Acetylcholinesterase inhibitors are widely used for a variety of medical, agricultural and public health purposes. Consequently, exposure is highly possible during lifetime. However, their systematic use raises concerns for the potential impact on the fetus and newborn since these substances may affect angiogenesis, the neonatal and maternal intensive care, neuroimmune function and response, mammary growth/lactation via cholinergic/non-cholinergic central and peripheral neuroendocrine pathways. New methodologies, neuroscientific technologies and research studies are needed to harness existing knowledge along with the proper management, availability for new acetylcholinesterase inhibitors, with stable pharmacodynamics and clinical outcomes.


Assuntos
Inibidores da Colinesterase , Embrião de Mamíferos/efeitos dos fármacos , Animais , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Embrião de Mamíferos/fisiologia , Humanos , Teratógenos/farmacologia
14.
Environ Res ; 166: 473-480, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29957500

RESUMO

The effect of carbon and silicon nanotubes (CNTs and SiNTs) and carbon nanofibers (CNFs) to microscopic marine algae Heterosigma akashiwo was studied, using algal growth inhibition for 3 days (acute effect) and 7 days (chronic effect) as toxicity endpoints. The criterion of the toxic effect was the statistically significant reduction of the number of algal cells in the exposed samples compared to the control. Samples did not demonstrate toxic effects at doses 1 mg/l and 10 mg/l. CNTs and SiNTs samples at 100 mg/l exhibited both acute and chronic toxic effects. We assume that the main cause of cell death in these samples was related to the mechanical damage of cell integrity. CNFs at concentrations of 100 mg/l did not inhibit algal growth, but cells with irregular shapes were observed, which were not observed after exposure to CNTs and SiNTs. Nickel impurities present in CNFs samples are presumably the main cause of observed cell deformations.


Assuntos
Microalgas/efeitos dos fármacos , Nanofibras/toxicidade , Nanotubos de Carbono/toxicidade , Silício/toxicidade
15.
Toxicol Rep ; 5: 224-230, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29854593

RESUMO

Despite the fact that environmental pollution due to motorcycle exhaust gases reports a great increase, motorcycle production exhibits a great increase through the last years. Countries of Asia and Africa are reported to be the major regions where two-wheeled vehicles are a major transportation mode, with tens of millions of units sold per year. Motorcycle exhaust particles are considered to be the major contributor to environmental pollution due to their airborne dispersion, containing great amount of polycyclic aromatic hydrocarbons (PAHs). This study aims at reporting an objective analysis of the main sources of the ambient air pollution as also particle size distribution and chemical composition analysis of particulate matter originated from the exhausts of two-wheeled vehicles used in the territory of Vladivostok, Russia. Various types of two-wheeled vehicles were examined (motorcycles, ATVs, scooters and wet bikes) using different types of engine and fuel system. Experimental results showed that there was no clear relation to the particle size distribution with the engine displacement of motorcycle and the number of strokes and the fuel system. Instead, there were reported two clear assumptions. The first one is that regarding to the motorcycle brand, a few samples did not exhibit a great percentage of PM10 fraction. The second one is that more modern vehicles, that have a harmful gas afterburning system, are usually the source of an increased percentage of PM10 emitted particles. At last, it should be mentioned that the laser particle size analysis method is capable of determining the particle sizes after their agglomeration whereas the optical morphometry method allows to determine the real particle size of emissions. In conclusion, it can be pointed out that the agglomeration of particles can lead to the reduction in the toxicity of particles emissions originated from two wheeled-vehicles.

16.
Biomed Rep ; 8(2): 111-116, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29435268

RESUMO

Telomeres are repeated 5'-TTAGGG-3' sequences at the end of chromosomes, which maintain genomic stability. Their length is related to a number of diseases that affect humans. Apart from cancer, cardiovascular diseases, diabetes and other, telomere length has been associated with chronic diseases. Chronic mental illness includes various types of mental disorders with the most common being depression, schizophrenia and stress-anxiety. The aim of this review is to summarize the current state of knowledge on the role of telomeres in these disorders and to compare telomere length variations in patients receiving medication and patients not taking treatment. Most studies report reduced telomere length in patients suffering from mental disorders, compared to the general population. Since the factors that can affect telomere length are various, more experiments and investigations are required to understand the general impact of different factors on telomere length.

17.
Graefes Arch Clin Exp Ophthalmol ; 255(12): 2375-2380, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28963579

RESUMO

PURPOSE: Intravitreal delivery of non-steroidal anti-inflammatory drugs could be an effective way to treat macular edema caused by posterior segment inflammation. In this study, we evaluated the intravitreal bioavailability and anti-inflammatory efficacy of flurbiprofen in rabbit eyes. METHODS: For pharmacokinetics, 0.1 ml of 7.66 mg/ml flurbiprofen solution was injected intravitreally and vitreous drug levels were analyzed at specific time points using LC-MS technique. For efficacy, 100 ng lipopolysaccharide of E.coli was injected intravitreally in rabbits to induce inflammation. The animals were separated in three groups and received intraocular flurbiprofen, dexamethasone and PBS to serve as control. Complete ocular examination and total cell count in aqueous fluid were determined to evaluate the extent of inflammation. Eyes were then enucleated for histopathology analysis. The efficacy in the uveitis model was determined by clinical signs of inflammation, total leukocyte count and histology findings. RESULTS: No adverse events were observed during pharmacokinetic assessment. No signs of inflammation, hemorrhage or retina detachment were detected. The recovery of flurbiprofen from vitreous samples was 92.6%. The half-life of flurbiprofen was estimated to be 1.92 h with an elimination constant rate (K) of 0.36. Treatment with intraocular injections of flurbiprofen and dexamethasone significantly reduced total leukocyte count in a manner comparable to dexamethasone [reduction of 96.84% (p < 0.05) and 97.44% (p < 0.05), respectively]. Histologic studies demonstrated significantly less signs of ocular inflammation after flurbiprofen injection compared to control eyes. CONCLUSIONS: Flurbiprofen is effective in suppressing inflammation in this experimental uveitis model. In our experimental setting, intravitreal flurbiprofen seem to have a therapeutic result comparable to dexamethasone. However, the half-life of the drug remains short, necessitating further research to prolong its presence in the vitreous cavity.


Assuntos
Endoftalmite/complicações , Flurbiprofeno/farmacocinética , Edema Macular/tratamento farmacológico , Corpo Vítreo/metabolismo , Animais , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacocinética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Endoftalmite/tratamento farmacológico , Endoftalmite/metabolismo , Flurbiprofeno/administração & dosagem , Injeções Intravítreas , Edema Macular/diagnóstico , Edema Macular/etiologia , Oftalmoscopia , Segmento Posterior do Olho , Coelhos , Resultado do Tratamento , Corpo Vítreo/patologia
18.
Exp Ther Med ; 13(6): 2960-2968, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28587367

RESUMO

The aim of the present study was to examine the seasonality of hypospadias in Greece in an attempt to elucidate the aetiology. All boys born between 1991-1998, who underwent hypospadias repair at 'Aghia Sophia' Children's Hospital, Athens (n=542) were analysed. All Greek live-born males during the same period (population at risk; m=421,175) served as the controls. Seasonality by month of birth was evaluated with specific statistical tools. Meteorological parameters were also analysed. All tests yielded significant results, suggesting a simple harmonic prevalence pattern (highest/lowest: autumn, peak in October/spring, trough in April). Therefore, the first trimester of hypospadiac gestations coincides more frequently with winter. Meteorological parameters varied seasonally (maximal sunlight; air temperature in summer/minimal in winter, maximal rainfall in winter/minimal in summer) and were strongly associated pairwise. Hypospadiac birth prevalence follows a simple harmonic seasonal pattern and is associated with that of cryptorchidism in Greece. The coincidence of the first or third trimester of a potentially genetically influenced gestation with winter could lead to the phenotypic expression of hypospadias or cryptorchidism, respectively. The potential role of a cyclic-varied androgen-production stimulator, such as human chorionic gonadotrophin may be speculated. The seasonality of a common environmental factor acting directly/indirectly may contribute to these patterns, and possibly to the common pathogenesis of these congenital malformations.

19.
Hum Exp Toxicol ; 36(6): 554-564, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28539089

RESUMO

In real life, consumers are exposed to complex mixtures of chemicals via food, water and commercial products consumption. Since risk assessment usually focuses on individual compounds, the current regulatory approach doesn't assess the overall risk of chemicals present in a mixture. This study will evaluate the cumulative toxicity of mixtures of different classes of pesticides and mixtures of different classes of pesticides together with food additives (FAs) and common consumer product chemicals using realistic doses after long-term exposure. Groups of Sprague Dawley (CD-SD) rats (20 males and 20 females) will be treated with mixtures of pesticides or mixtures of pesticides together with FAs and common consumer product chemicals in 0.0, 0.25 × acceptable daily intake (ADI)/tolerable daily intake (TDI), ADI/TDI and 5 × ADI/TDI doses for 104 weeks. All animals will be examined every day for signs of morbidity and mortality. Clinical chemistry hematological parameters, serum hormone levels, biomarkers of oxidative stress, cardiotoxicity, genotoxicity, urinalysis and echocardiographic tests will be assessed periodically at 6 month intervals. At 3-month intervals, ophthalmological examination, test for sensory reactivity to different types of stimuli, together with assessment of learning abilities and memory performance of the adult and ageing animals will be conducted. After 24 months, animals will be necropsied, and internal organs will be histopathologically examined. If the hypothesis of an increased risk or a new hazard not currently identified from cumulative exposure to multiple chemicals was observed, this will provide further information to public authorities and research communities supporting the need of replacing current single-compound risk assessment by a more robust cumulative risk assessment paradigm.


Assuntos
Aditivos Alimentares/toxicidade , Praguicidas/toxicidade , Medição de Risco/métodos , Animais , Simulação por Computador , Consenso , Exposição Ambiental , Feminino , Contaminação de Alimentos , Humanos , Masculino , Ratos Sprague-Dawley
20.
Food Chem Toxicol ; 96: 273-9, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27539747

RESUMO

The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Polímeros/química , Pirrolidinonas/toxicidade , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/toxicidade , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Nanopartículas/química , Pirrolidinonas/administração & dosagem , Testes de Toxicidade Aguda
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