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1.
Nanomaterials (Basel) ; 13(4)2023 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-36839135

RESUMO

Titanium dioxide nanoparticles (TiO2 NPs) are used in a wide range of applications. Although inhalation of NPs is one of the most important toxicologically relevant routes, experimental studies on potential harmful effects of TiO2 NPs using a whole-body inhalation chamber model are rare. In this study, the profile of lymphocyte markers, functional immunoassays, and antioxidant defense markers were analyzed to evaluate the potential adverse effects of seven-week inhalation exposure to two different concentrations of TiO2 NPs (0.00167 and 0.1308 mg TiO2/m3) in mice. A dose-dependent effect of TiO2 NPs on innate immunity was evident in the form of stimulated phagocytic activity of monocytes in low-dose mice and suppressed secretory function of monocytes (IL-18) in high-dose animals. The effect of TiO2 NPs on adaptive immunity, manifested in the spleen by a decrease in the percentage of T-cells, a reduction in T-helper cells, and a dose-dependent decrease in lymphocyte cytokine production, may indicate immunosuppression in exposed mice. The dose-dependent increase in GSH concentration and GSH/GSSG ratio in whole blood demonstrated stimulated antioxidant defense against oxidative stress induced by TiO2 NP exposure.

2.
Artigo em Inglês | MEDLINE | ID: mdl-36669817

RESUMO

As part of a large human biomonitoring study, we conducted occupational monitoring in a glass fibre factory in Slovakia. Shopfloor workers (n = 80), with a matched group of administrators in the same factory (n = 36), were monitored for exposure to glass fibres and to polycyclic aromatic hydrocarbons (PAHs). The impact of occupational exposure on chromosomal aberrations, DNA damage and DNA repair, immunomodulatory markers, and the role of nutritional and lifestyle factors, as well as the effect of polymorphisms in metabolic and DNA repair genes on genetic stability, were investigated. The (enzyme-modified) comet assay was employed to measure DNA strand breaks (SBs) and apurinic sites, oxidised and alkylated bases. Antioxidant status was estimated by resistance to H2O2-induced DNA damage. Base excision repair capacity was measured with an in vitro assay (based on the comet assay). Exposure of workers to fibres was low, but still was associated with higher levels of SBs, and SBs plus oxidised bases, and higher sensitivity to H2O2. Multivariate analysis showed that exposure increased the risk of high levels of SBs by 20%. DNA damage was influenced by antioxidant enzymes catalase and glutathione S-transferase (measured in blood). DNA repair capacity was inversely correlated with DNA damage and positively with antioxidant status. An inverse correlation was found between DNA base oxidation and the percentage of eosinophils (involved in the inflammatory response) in peripheral blood of both exposed and reference groups. Genotypes of XRCC1 variants rs3213245 and rs25487 significantly decreased the risk of high levels of base oxidation, to 0.50 (p = 0.001) and 0.59 (p = 0.001), respectively. Increases in DNA damage owing to glass fibre exposure were significant but modest, and no increases were seen in chromosome aberrations or micronuclei. However, it is of concern that even low levels of exposure to these fibres can cause significant genetic damage.


Assuntos
Antioxidantes , Exposição Ocupacional , Humanos , Monitoramento Biológico , Peróxido de Hidrogênio , Dano ao DNA , Reparo do DNA , Ensaio Cometa , Exposição Ocupacional/efeitos adversos , Aberrações Cromossômicas , DNA , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
3.
BMC Pediatr ; 22(1): 289, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35581625

RESUMO

BACKGROUND: Obesity and hypertension represent serious health issues affecting the pediatric population with increasing prevalence. Hypovitaminosis D has been suggested to be associated with arterial hypertension. Serotonin by modulating nitric oxide synthase affect blood pressure regulation. The biological mechanism by which vitamin D specifically regulates serotonin synthesis was recently described. The aim of this paper is to determine the associations between vitamin D, serotonin, and blood pressure in obese children. METHODS: One hundred and seventy-one children were enrolled in the prospective cross-sectional study. Two groups of children divided according to body mass index status to obese (BMI ≥95th percentile; n = 120) and non-obese (n = 51) were set. All children underwent office and ambulatory blood pressure monitoring and biochemical analysis of vitamin D and serotonin. Data on fasting glucose, insulin, HOMA, uric acid, and complete lipid profile were obtained in obese children. RESULTS: Hypertension was found only in the group of obese children. Compared to the control group, obese children had lower vitamin D and serotonin, especially in winter. The vitamin D seasonality and BMI-SDS were shown as the most significant predictors of systolic blood pressure changes, while diastolic blood pressure was predicted mostly by insulin and serotonin. The presence of hypertension and high-normal blood pressure in obese children was most significantly affected by vitamin D deficiency and increased BMI-SDS. CONCLUSIONS: Dysregulation of vitamin D and serotonin can pose a risk of the onset and development of hypertension in obese children; therefore, their optimization together with reducing body weight may improve the long-term cardiovascular health of these children.


Assuntos
Hipertensão , Resistência à Insulina , Obesidade Infantil , Deficiência de Vitamina D , Monitorização Ambulatorial da Pressão Arterial , Índice de Massa Corporal , Criança , Estudos Transversais , Humanos , Hipertensão/epidemiologia , Insulina , Obesidade Infantil/complicações , Obesidade Infantil/epidemiologia , Estudos Prospectivos , Serotonina , Vitamina D , Vitaminas
4.
Front Immunol ; 13: 874253, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547729

RESUMO

Copper oxide nanoparticles (CuO NPs) are increasingly used in various industry sectors. Moreover, medical application of CuO NPs as antimicrobials also contributes to human exposure. Their toxicity, including toxicity to the immune system and blood, raises concerns, while information on their immunotoxicity is still very limited. The aim of our work was to evaluate the effects of CuO NPs (number concentration 1.40×106 particles/cm3, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m3 continuously for 6 weeks. After six weeks of CuO NP inhalation, the content of copper in lungs and liver was significantly increased, while in kidneys, spleen, brain, and blood it was similar in exposed and control mice. Inhalation of CuO NPs caused a significant increase in proliferative response of T-lymphocytes after mitogenic stimulation and basal proliferative activity of splenocytes. CuO NPs significantly induced the production of IL-12p70, Th1-cytokine IFN-γ and Th2-cytokines IL-4, IL-5. Levels of TNF-α and IL-6 remained unchanged. Immune assays showed significantly suppressed phagocytic activity of granulocytes and slightly decreased respiratory burst. No significant differences in phagocytosis of monocytes were recorded. The percentage of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD19+ cell subsets in spleen, thymus, and lymph nodes did not differ between exposed and control animals. No changes in hematological parameters were found between the CuO NP exposed and control groups. The overall antioxidant protection status of the organism was expressed by evaluation of GSH and GSSG concentrations in blood samples. The experimental group exposed to CuO NPs showed a significant decrease in GSH concentration in comparison to the control group. In summary, our results indicate that sub-chronic inhalation of CuO NPs can cause undesired modulation of the immune response. Stimulation of adaptive immunity was indicated by activation of proliferation and secretion functions of lymphocytes. CuO NPs elicited pro-activation state of Th1 and Th2 lymphocytes in exposed mice. Innate immunity was affected by impaired phagocytic activity of granulocytes. Reduced glutathione was significantly decreased in mice exposed to CuO NPs.


Assuntos
Cobre , Nanopartículas , Imunidade Adaptativa , Animais , Antioxidantes , Cobre/toxicidade , Citocinas , Camundongos , Nanopartículas/toxicidade , Óxidos
5.
Biomed Pharmacother ; 146: 112562, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35062058

RESUMO

Multidirectional health-promoting activities of some plant-derived substances make them candidates for drugs used in diabetes and its complications such as osteoporosis. Berberine is a compound for which both antidiabetic and antiosteoporotic effects have been documented. The aim of the study was to investigate the effects of berberine on the skeletal disorders induced by experimental type 1 diabetes in rats. The experiments were performed on 3-month-old female rats, divided into three groups: I - healthy control rats, II - diabetic control rats, III - diabetic rats receiving berberine. Diabetes was induced by a single streptozotocin injection. Berberine administration (50 mg/kg/day p.o.) started two weeks later and lasted four weeks. Serum bone turnover markers and other biochemical parameters, bone mass and mineralization, histomorphometric parameters and mechanical properties were studied. Diabetes induced strong disorders of bone turnover, bone microarchitecture, and strength of cancellous bone. Berberine counteracted the effect of diabetes on the bone formation marker (osteocalcin) concentration, the growth plate, and some parameters of cancellous bone microarchitecture, but did not improve bone mineralization and bone mechanical properties in the diabetic rats. The lack of effect of berberine on bone quality does not support its use in the prevention of diabetes-induced bone damage.


Assuntos
Berberina/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Lâmina de Crescimento/efeitos dos fármacos , Animais , Berberina/administração & dosagem , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Feminino , Osteoporose/prevenção & controle , Ratos , Ratos Wistar , Estreptozocina/administração & dosagem
6.
Biol Trace Elem Res ; 200(2): 624-634, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33656659

RESUMO

Osteoporosis is a growing public health issue for an aging society. Previous studies have found both beneficial and detrimental effects of obesity on bone health. The purpose of this study was to investigate the impact of estrogen deficiency and physical activity on bone and blood concentrations of macrominerals (Ca, P, and Mg) and microminerals (Zn, Se, Cu, and Fe) in a high-fat diet-induced obesity rat model. Forty-eight female Wistar rats were divided into six groups: sham-operated and ovariectomized rats that received a standard diet (SD), high-fat diet (HFD), or HFD accompanied by physical exercise. The effect of ovariectomy on bone minerals varied with diet. Ovariectomy significantly decreased femoral Ca and Mg in sedentary rats receiving a SD; femoral Se, Cu, Zn, and Fe in sedentary rats on HFD; and plasma Fe in both sedentary rats on SD and exercising rats on HFD. The interaction of ovariectomy and diet had the strongest impact on Mg and Se concentrations in femur. In ovariectomized rats, HFD showed to have a protective effect on bone mineralization (femoral Ca and Mg), and a negative one on antioxidant microminerals (femoral Se, Cu, and Zn). Physical activity reduced the decline of Se, Cu, Zn, and Fe in the femur of ovariectomized rats on HFD. In the current state of knowledge, it is difficult to suggest if decreased femoral levels of antioxidant microminerals may contribute to the pathophysiology of osteoporosis in obese individuals or just reflect the mineral status in the body.


Assuntos
Dieta Hiperlipídica , Obesidade , Animais , Densidade Óssea , Dieta Hiperlipídica/efeitos adversos , Feminino , Humanos , Minerais , Ovariectomia , Ratos , Ratos Wistar
7.
Nanomaterials (Basel) ; 11(7)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203551

RESUMO

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat's liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects.

9.
Food Chem Toxicol ; 136: 110954, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31707033

RESUMO

Due to the growing number of applications of cadmium oxide nanoparticles (CdO NPs), there is a concern about their potential deleterious effects. The objective of our study was to investigate the effect of CdO NPs on the immune response, renal and intestine oxidative stress, blood antioxidant defence, renal fibrotic response, bone density and mineral content. Six-week-old female ICR mice were exposed to CdO NPs for 6 weeks by inhalation (particle size: 9.82 nm, mass concentration: 31.7 µg CdO/m3, total deposited dose: 0.195 µg CdO/g body weight). CdO NPs increased percentage of thymus CD3e+CD8a+ cells and moderately enhanced splenocyte proliferation and production of cytokines and chemokines. CdO NPs elevated pro-fibrotic factors (TGF-ß2, α-SMA and collagen I) in the kidney, and concentrations of AGEs in the intestine. The ratio of GSH and GSSG in blood was slightly reduced. Exposure to CdO NPs resulted in 10-fold higher Cd concentration in tibia bones. No differences were found in bone mass density, mineral content, bone area values, bone concentrations of Ca, P, Mg and Ca/P ratio. Our findings indicate stimulation of immune/inflammatory response, oxidative stress in the intestine, starting fibrotic response in kidneys and accumulation of CdO NPs in bones of mice.


Assuntos
Compostos de Cádmio/toxicidade , Fibrose/induzido quimicamente , Imunidade Celular/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Óxidos/toxicidade , Tíbia/efeitos dos fármacos , Administração por Inalação , Animais , Compostos de Cádmio/administração & dosagem , Citocinas/metabolismo , Feminino , Intestinos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Linfonodos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Camundongos Endogâmicos ICR , Óxidos/administração & dosagem , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos
10.
Ann Noninvasive Electrocardiol ; 24(6): e12684, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31368226

RESUMO

BACKGROUND: According to current guidelines, the main indications for PCI in patients with STEMI are ST-segment deviations and defined time from the onset of symptoms. Negative T wave at admission can be a sign of prolonged ischemia or spontaneous reperfusion. In both situations, the urgent intervention is questionable. We evaluated the infarct size and in-hospital mortality in STEMI patients with negative T wave in cases of primary PCI strategy compared with conservative treatment. METHODS: A retrospective analysis of 116 STEMI patients with negative T wave at the presenting ECG was performed. Sixty-eight patients (59%) underwent primary PCI strategy (PCI group), and 48 (41%) were treated conservatively (non-PCI group). The infarct size estimated by using the Selvester score, and in-hospital mortality were evaluated. RESULTS: The difference between Selvester score values at admission and at discharge in the non-PCI group was statistically significant (1.48; 95% CI 0.694-2.27), while no significant difference was observed in the PCI group (-0.07; 95% CI -0.546-0.686). The in-hospital mortality was higher in the non-PCI group; however, the numbers were relatively small: PCI 2 (2.9%) and non-PCI 5 (10.4%). CONCLUSION: In this study, we showed a reduction in the infarct size estimated by Selvester score in STEMI patients with negative T wave who were treated conservatively, while there was no significant change in the infarct size after primary PCI strategy. The higher mortality in patients treated conservatively could be attributed to higher age and comorbidities in the non-PCI group. It seems that conservative treatment strategy might be an option in STEMI patients with negative T wave.


Assuntos
Tratamento Conservador/métodos , Eletrocardiografia/métodos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
11.
Arch Toxicol ; 93(4): 1095-1139, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30756133

RESUMO

In 2012, a controversial study on the long-term toxicity of a Roundup herbicide and the glyphosate-tolerant genetically modified (GM) maize NK603 was published. The EC-funded G-TwYST research consortium tested the potential subchronic and chronic toxicity as well as the carcinogenicity of the glyphosate-resistant genetically modified maize NK603 by performing two 90-day feeding trials, one with GM maize inclusion rates of 11 and 33% and one with inclusion rates of up to 50%, as well as a 2-year feeding trial with inclusion rates of 11 and 33% in male and female Wistar Han RCC rats by taking into account OECD Guidelines for the testing of chemicals and EFSA recommendations on the safety testing of whole-food/feed in laboratory animals. In all three trials, the NK603 maize, untreated and treated once with Roundup during its cultivation, and the conventional counterpart were tested. Differences between each test group and the control group were evaluated. Equivalence was assessed by comparing the observed difference to differences between non-GM reference groups in previous studies. In case of significant differences, whether the effects were dose-related and/or accompanied by changes in related parameters including histopathological findings was evaluated. It is concluded that no adverse effects related to the feeding of the NK603 maize cultivated with or without Roundup for up to 2 years were observed. Based on the outcome of the subchronic and combined chronic toxicity/carcinogenicity studies, recommendations on the scientific justification and added value of long-term feeding trials in the GM plant risk assessment process are presented.


Assuntos
Ração Animal/normas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Alimentos Geneticamente Modificados , Glicina/análogos & derivados , Herbicidas/toxicidade , Plantas Geneticamente Modificadas/efeitos dos fármacos , Zea mays , Animais , Testes de Carcinogenicidade , Resistência a Medicamentos/genética , Feminino , Glicina/toxicidade , Masculino , Plantas Geneticamente Modificadas/genética , Ratos Wistar , Testes de Toxicidade Crônica , Testes de Toxicidade Subcrônica , Zea mays/efeitos dos fármacos , Zea mays/genética , Glifosato
12.
Eur J Nutr ; 58(8): 3199-3206, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30448878

RESUMO

PURPOSE: To determine the DNA protective effects of a standard coffee beverage in comparison to water consumption. METHODS: The single-blind, randomised controlled study with parallel design included healthy women (n = 50) and men (n = 50) recruited from the general Central European population. The subjects were randomised in a coffee and a control group, with stratification for sex and body mass index. The study comprised two periods of 4 weeks: a preconditioning period, with daily consumption of at least 500 ml water but no coffee, nor tea, nor any other caffeine-containing product. During the subsequent intervention period the coffee group consumed 500 ml of freshly brewed dark roast coffee blend per day, the control group consumed water instead. On the last day of each period, blood was drawn and analysed by comet assay (single-cell gel electrophoresis) to assess the level of DNA damage (strand breakage). RESULTS: At the end of the intervention period the mean level of DNA strand breaks in the coffee group has decreased in comparison to the control group [difference in means 0.23% TI (tail intensity), p = 0.028]. The mean change from baseline (delta value) was - 23% in the coffee group (p = 0.0012). Effects of coffee intake were similar for men and women. During intervention, neither group showed any significant change in body weight or calorie intake. CONCLUSIONS: Our results indicate that regular consumption of a dark roast coffee blend has a beneficial protective effect on human DNA integrity in both, men and women.


Assuntos
Café , Dano ao DNA/efeitos dos fármacos , Adulto , Culinária , Europa (Continente) , Feminino , Temperatura Alta , Humanos , Masculino , Método Simples-Cego
13.
J Electrocardiol ; 51(6): 1085-1089, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30497735

RESUMO

Both obesity and menopause are significant cardiovascular risk factors. In postmenopausal women the protective effect of estrogens is reduced and menopause is frequently associated with occurrence of other significant cardiovascular factors including obesity. This study was focused on evaluating the effect of obesity on the QRS complex in pre- and postmenopausal women. We present results of analysis of 199 electrocardiograms of pre- and postmenopausal women analyzed in relation to the body mass index within normal limits (BMI 20 to 24.9 kg/m2) and obesity (BMI > 30 kg/m2), respectively. Obesity in premenopausal women and menopause significantly affected both the electrical axis (EA) and maximum QRS spatial vector magnitude (QRSmax). The highest QRSmax and electrical axis values were observed in premenopausal lean women, and they were significantly higher as than in the premenopausal obese women, postmenopausal lean and obese women (QRSmax: 1.66 ±â€¯0.4 mV, 1.17 ±â€¯0.35 mV, 1.4 ±â€¯0.46 mV, and 1.35 ±â€¯0.39 mV, resp.). (EA: 56.4 ±â€¯18.0°, 38.22 ±â€¯18.38°, 45.82 ±â€¯18.63°, and 36.75 ±â€¯17.51°). The differences between obese premenopausal women, lean and obese postmenopausal women were not statistically significant. These differences were reflected in 12-lead ECG amplitude. The presence of additional cardiovascular risk factors did not affect the ECG parameters. Obesity significantly affected QRS complex in premenopausal women. This effect was comparable with the effect of menopause. Because all QRS complex changes were within normal limits, these results suggest that ECG evaluation in women should go beyond traditional diagnostic categories and consider the relationship between ECG changes and two cardiovascular risk factors - obesity and menopause.


Assuntos
Eletrocardiografia , Obesidade/fisiopatologia , Pós-Menopausa/fisiologia , Pré-Menopausa/fisiologia , Adulto , Idoso , Índice de Massa Corporal , Doenças Cardiovasculares , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
14.
Exp Clin Endocrinol Diabetes ; 126(5): 309-315, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29117621

RESUMO

We investigated whether metabolically healthy normal weight adults with central obesity display worse cardiometabolic profile compared with their centrally lean counterparts. This retrospective, cross-sectional study, comprised 1 135 subjects (64% females) aged 18-to-81 years, presenting ≤2 components of metabolic syndrome. They were classified as centrally lean (waist-to-height ratio (WHtR)<0.5 and waist circumference<80 cm in females and<94 cm in males) or presenting central obesity (WHtR ≥0.5, regardless of waist circumference). Data on blood pressure, glucose homeostasis, lipid profile, renal function, high-sensitive C-reactive protein (hsCRP), uric acid, adiponectin, leptin, and soluble receptor for advanced glycation end products were compared between the groups, separately in males and females. 5.7% of males and 6.9% of females presented WHtR ≥0.5. Compared with centrally lean subjects, those with central obesity had higher BMI-adjusted fasting plasma glucose (p<0.001), and leptin levels (p<0.05); females also presented higher blood pressure (p<0.001), while males had higher hsCRP concentrations (p=0.021). These changes associated with significantly higher BMI-adjusted odds to present fasting plasma glucose >5.6 mmol/l in both genders, higher odds to present hsCRP >3 mg/l in males, and those to present elevated blood pressure in females. Our analysis suggests that in metabolically healthy normal weight subjects WHtR ≥0.5 might indicate "early increased health risk".


Assuntos
Glicemia/análise , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Peso Corporal/fisiologia , Proteína C-Reativa/análise , Leptina/sangue , Obesidade Abdominal/sangue , Obesidade Abdominal/fisiopatologia , Razão Cintura-Estatura , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Adulto Jovem
15.
Nutrients ; 9(11)2017 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-29084147

RESUMO

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.


Assuntos
Osso e Ossos/efeitos dos fármacos , Cafeína/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Músculo Esquelético/efeitos dos fármacos , Animais , Osso e Ossos/fisiologia , Café/química , Diabetes Mellitus Experimental/complicações , Relação Dose-Resposta a Droga , Feminino , Músculo Esquelético/fisiologia , Niacinamida , Osteoporose/tratamento farmacológico , Osteoporose/etiologia , Ratos , Ratos Wistar
16.
Artigo em Inglês | MEDLINE | ID: mdl-28696349

RESUMO

The age-related changes and hormonal deprivation in postmenopausal women are associated with the immune response alteration. The excessive fat accumulation, local and systemic inflammation may lead to dysregulation in immune function and relevant health problems, including obesity and osteoporosis. We analyzed the expression of cell surface markers in the venous blood specimens, stained with fluorophores-conjugated monoclonal antibodies and analysed by multicolour flow cytometry. The significant changes of cytotoxic, naive, and memory T-lymphocytes, plasmacytoid dendritic cells (DCs) were in postmenopausal women versus fertile women. Body mass index (BMI) affected markedly the cell surface expression of CD265/RANK. Osteoporosis is linked to reduced percentage of plasmacytoid DCs, and elevated natural Treg cells (p < 0.05). The confounding factors such as women age, BMI, bone mineral density (BMD), waist size and tissue fat affect the expression of RANK on myeloid DCs and CD40L on T-lymphocytes that might be the immunophenotypic modulators after menopause.


Assuntos
Linfócitos B/fisiologia , Obesidade/metabolismo , Osteoporose Pós-Menopausa/metabolismo , Pós-Menopausa/fisiologia , Linfócitos T/fisiologia , Adulto , Idoso , Biomarcadores , Densidade Óssea/fisiologia , Feminino , Humanos , Pessoa de Meia-Idade
17.
Arch Toxicol ; 90(10): 2531-62, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27439414

RESUMO

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu ) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure.


Assuntos
Ração Animal , Alimentos Geneticamente Modificados/toxicidade , Nível de Saúde , Plantas Geneticamente Modificadas/toxicidade , Zea mays/genética , Ração Animal/normas , Ração Animal/toxicidade , Animais , Feminino , Masculino , Ratos Endogâmicos , Medição de Risco , Testes de Toxicidade Crônica
18.
Nutrients ; 8(3): 133, 2016 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-26950142

RESUMO

Diabetes increases bone fracture risk. Trigonelline, an alkaloid with potential antidiabetic activity, is present in considerable amounts in coffee. The aim of the study was to investigate the effects of trigonelline on experimental diabetes-induced disorders in the rat skeletal system. Effects of trigonelline (50 mg/kg p.o. daily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of trigonelline administration, received streptozotocin (60 mg/kg i.p.) or streptozotocin after nicotinamide (230 mg/kg i.p.). Serum bone turnover markers, bone mineralization, and mechanical properties were studied. Streptozotocin induced diabetes, with significant worsening of bone mineralization and bone mechanical properties. Streptozotocin after nicotinamide induced slight glycemia increases in first days of experiment only, however worsening of cancellous bone mechanical properties and decreased vertebral bone mineral density (BMD) were demonstrated. Trigonelline decreased bone mineralization and tended to worsen bone mechanical properties in streptozotocin-induced diabetic rats. In nicotinamide/streptozotocin-treated rats, trigonelline significantly increased BMD and tended to improve cancellous bone strength. Trigonelline differentially affected the skeletal system of rats with streptozotocin-induced metabolic disorders, intensifying the osteoporotic changes in streptozotocin-treated rats and favorably affecting bones in the non-hyperglycemic (nicotinamide/streptozotocin-treated) rats. The results indicate that, in certain conditions, trigonelline may damage bone.


Assuntos
Alcaloides/toxicidade , Coffea/química , Complicações do Diabetes/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/toxicidade , Osteoporose/induzido quimicamente , Extratos Vegetais/toxicidade , Alcaloides/isolamento & purificação , Animais , Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Complicações do Diabetes/sangue , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/induzido quimicamente , Feminino , Fêmur/efeitos dos fármacos , Fêmur/fisiopatologia , Hipoglicemiantes/isolamento & purificação , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/fisiopatologia , Niacinamida , Osteoporose/sangue , Osteoporose/fisiopatologia , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Medição de Risco , Sementes , Estreptozocina , Tíbia/efeitos dos fármacos , Tíbia/fisiopatologia , Suporte de Carga
19.
PLoS One ; 10(6): e0131753, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26120828

RESUMO

INTRODUCTION: Hypovitaminosis D associates with obesity, insulin resistance, hypertension, and dyslipoproteinemia. We asked whether the presence of multiple cardiometabolic risk factors, and which particular combination, exerts additive negative effects on 25(OH)D3 levels; and whether 25(OH)D3 levels associate with markers of inflammation and oxidative stress. SUBJECTS AND METHODS: In non-diabetic medication-free adults central obesity (waist-to-height ratio > 0.5); elevated blood pressure (systolic BP≥130 mm Hg and/or diastolic BP ≥85 mm Hg); increased atherogenic risk (log(TAG/HDL) ≥ 0.11); and insulin resistance (QUICKI < 0.322) were considered as cardiometabolic risk factors. 25(OH)D3 status was classified as deficiency (25(OH)D3 ≤20 ng/ml); insufficiency (levels between 20-to-30 ng/ml), or as satisfactory (>30 ng/ml). Plasma adipokines, inflammatory and oxidative stress markers, advanced glycation end-products, and their soluble receptor were determined. RESULTS: 162 subjects were cardiometabolic risk factors-free, 162 presented increased (i.e. 1 or 2), and 87 high number (i.e. 3 or 4) of cardiometabolic risk factors. Mean 25(OH)D3 decreased with rising number of manifested risk factors (36 ± 14 ng/ml, 33 ± 14 ng/ml, and 31 ± 15 ng/ml, respectively; pANOVA: 0.010), while prevalence of hypovitaminosis D did not differ significantly. Elevated blood pressure and insulin resistance appeared as significant determinants of hypovitaminosis D. Subjects presenting these risk factors concurrently displayed the lowest 25(OH)D3 levels (29 ± 15 ng/ml). Plasma adipokines, inflammatory and oxidative stress markers, advanced glycation end-products, and their soluble receptor generally differed significantly between the groups, but only advanced oxidation protein products and advanced glycation end-products associated fluorescence of plasma showed significant independent association with 25(OH)D3 levels. CONCLUSION: In apparently healthy adults increasing number of cardiometabolic risk factors associates with poorer 25(OH)D3 status, while the association between 25(OH)D3 status and inflammatory or oxidative stress markers remains equivocal.


Assuntos
Adipocinas/sangue , Biomarcadores/sangue , Produtos Finais de Glicação Avançada/sangue , Saúde , Inflamação/sangue , Estresse Oxidativo , Vitamina D/sangue , Adulto , Pressão Sanguínea , Calcifediol/sangue , Estudos de Coortes , Árvores de Decisões , Feminino , Humanos , Masculino , Fatores de Risco
20.
Arch Toxicol ; 88(12): 2289-314, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25270621

RESUMO

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu ) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event.


Assuntos
Ração Animal , Alimentos Geneticamente Modificados/toxicidade , Plantas Geneticamente Modificadas/toxicidade , Zea mays/genética , Administração Oral , Ração Animal/normas , Ração Animal/toxicidade , Animais , Peso Corporal , Qualidade de Produtos para o Consumidor , Dieta , Feminino , Masculino , Tamanho do Órgão , Ratos Endogâmicos , Projetos de Pesquisa , Medição de Risco , Testes de Toxicidade Subcrônica
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