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.
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 1.40×10
particles/cm
, geometric mean diameter 20.4 nm) on immune/inflammatory response and antioxidant defense in mice exposed to 32.5 µg CuO/m
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.
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.
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.
Titanium dioxide nanoparticles (TiO
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 TiO
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 TiO
NPs (0.00167 and 0.1308 mg TiO
/m
) in mice. A dose-dependent effect of TiO
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 TiO
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 TiO
NP exposure.
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.
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.
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.
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.
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.
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.
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.
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.
Abstract Objective This study was undertaken to evaluate the nature and onset of changes in the QRS complex in the offspring of patients with diabetes mellitus (DM) and metabolic syndrome (MetS). ...Methods and Methods A total of 529 subjects, divided into 5 groups, were included in the study: (i) group DM (n = 92), patients with DM; (ii) group MetS (n = 125), patients with MetS; (iii) group O-DM (n = 109), offspring of patients with DM; (iv) group O-MetS (n = 122), offspring of patients with MetS; and (v) group HO (n = 81), offspring of healthy subjects. QRS parameters analyzed included amplitude, maximum QRS spatial vector magnitude, electrical axis (EA), and 3 electrocardiogram (ECG) criteria for left ventricular hypertrophy based on amplitude criteria: Sokolow-Lyon index, Cornell voltage, and Gubner criterion. Results Patients with DM and MetS showed a significant leftward shift of the EA when compared with the control group. A modest but significant leftward shift of EA was also observed in both offspring groups. These EA and maximum QRS spatial vector magnitude changes were reflected in the individual leads of the 12-lead ECG. The prevalence of a positive diagnosis by accepted electrocardiographic criteria (ECG left ventricular hypertrophy) was low. Conclusion Patients with DM and MetS displayed significant changes in QRS complex that suggest depolarization sequence deterioration. Similar changes were observed also in the offspring of patients with DM and MetS, which suggests early subclinical cardiovascular damage. These findings have implications for prevention, early diagnosis, and treatment in the offspring of patients with DM and MetS.
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.
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.
•Berberine increased bone formation and slightly ameliorated cancellous bone microstructure disorders in diabetic rats.•Berberine did not favorably affect bone composition and mechanical properties in diabetic rats.•Berberine favorably affected the epiphyseal cartilage (growth plate) of diabetic rats.•The lack of berberine effect on bone quality does not support its use in the prevention of diabetes-induced bone damage.
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