Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

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

Impact of ovariectomy, high fat diet, and lifestyle modifications on oxidative/antioxidative status in the rat liver

Aim To estimate the impact of high fat diet and estrogen deficiency on the oxidative and antioxidative status in the liver of the ovariectomized rats, as well as the ameliorating effect of physical activity or consumption of functional food containing bioactive compounds with antioxidative properties on oxidative damage in the rat liver. Methods The study was conducted from November 2012 to April 2013. Liver oxidative damage was determined by lipid peroxidation levels expressed in terms of thiobarbituric acid reactive substances (TBARS), while liver antioxidative status was determined by catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) activities, and glutathione (GSH) content. Sixty-four female Wistar rats were divided into eight groups: sham operated and ovariectomized rats that received either standard diet, high fat diet, or high fat diet supplemented with cereal selenized onion biscuits or high fat diet together with introduction of physical exercise of animals. Results High fat diet significantly increased TBARS content in the liver compared to standard diet (P = 0.032, P = 0.030). Furthermore, high fat diet decreased the activities of CAT, GR, and GST, as well as the content of GSH (P < 0.050). GPx activity remained unchanged in all groups. Physical activity and consumption of cereal selenized onion biscuits showed protective effect through increased GR activity in sham operated rats (P = 0.026, P = 0.009), while in ovariectomized group CAT activity was increased (P = 0.018) in rats that received cereal selenized onion biscuits. Conclusion Feeding rats with high fat diet was accompanied by decreased antioxidative enzyme activities and increased lipid peroxidation. Bioactive compounds of cereal selenized onion biscuits showed potential to attenuate the adverse impact of high fat diet on antioxidative statu

Effects of high fat diet, ovariectomy, and physical activity on leptin receptor expression in rat brain and white fat tissue

Aim To evaluate in a rat animal model whether ovariectomy, high fat diet (HFD), and physical activity in the form of running affect leptin receptor (Ob-R) distribution in the brain and white fat tissue compared to sham (Sh) surgery, standard diet (StD), and sedentary conditions. Methods The study included 48 female laboratory Wistar rats (4 weeks old). Following eight weeks of feeding with standard or HFD, rats were subjected to either OVX or Sh surgery. After surgery, all animals continued StD or HFD for the next 10 weeks. During these 10 weeks, ovariectomy and Sh groups were subjected to physical activity or sedentary conditions. Free-floating immunohistochemistry and Western blot methods were carried out to detect Ob-R in the brain and adipose tissue. Results StD-ovariectomy-sedentary group had a greater number of Ob-R positive neurons in lateral hypothalamic nuclei than StD-Sh-sedentary group. There was no difference in Ob-R positive neurons in arcuatus nuclei between all groups. Ob-R distribution in the barrel cortex was higher in HFD group than in StD group. Ob-R presence in perirenal and subcutaneous fat was decreased in StD-ovariectomy group. Conclusion HFD and ovariectomy increased Ob-R distribution in lateral hypothalamic nuclei, but there was no effect on arcuatus nuclei. Our results are first to suggest that HFD, ovariectomy, and physical activity affect Ob-R distribution in the barrel cortex, which might be correlated with the role of Ob-R in election of food in rats

Plasma 25(OH)D₃ concentration according to absence or presence of cardiometabolic risk factors.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated blood pressure (BP): systolic BP ≥130 mm Hg and/or diastolic BP ≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87). Data are given as interquartile range (box), 5^th and 95^th percentile (whiskers). Statistical evaluation was performed on natural ln-transformed data. ANOVA: p<0.001, Scheffe’s post hoc test p indicated.</p

Cohort characteristics: inflammatory and oxidative stress markers, adipokines and advanced glycation end products.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated BP: systolic BP (SBP)≥130 mm Hg and/or diastolic BP (DBP)≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87); hsCRP: high sensitive C-reactive protein; IL-6: interleukine-6; hsTNF-α: high sensitive tumor necrosis factor-α; CML: N^ε-(carboxymethyl)lysine; Alb: albumin; AGE-Fl: advanced glycation end products associated fluorescence of plasma; AU: arbitrary units; AOPP: advanced oxidation protein products; sRAGE: soluble receptor for advanced glycation end products</p><p>*: p<0.05 vs. cardiometabolic risk factors free subjects</p><p>**: p<0.01 vs. cardiometabolic risk factors free subjects</p><p>***: p<0.001 vs. cardiometabolic risk factors free subjects</p><p>+: p<0.05 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>++: p<0.01 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>+++: p<0.001 vs. subjects presenting 1 or 2 cardiometabolic risk factors; <i>italics</i>: statistical evaluation performed on logarithmically transformed data</p><p>Cohort characteristics: inflammatory and oxidative stress markers, adipokines and advanced glycation end products.</p

Cohort characteristics: anthropometric data, blood pressure, standard blood chemistry variables and 25(OH)D₃ levels.

<p>Central obesity: waist-to-height ration >0.5 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref031" target="_blank">31</a>]; elevated BP: systolic BP (SBP)≥130 mm Hg and/or diastolic BP (DBP)≥85 mm Hg; increased atherogenic risk: AIP≥0.11 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0131753#pone.0131753.ref029" target="_blank">29</a>]; and insulin resistance: QUICKI<0.322 were considered as factors indicated increased cardiometabolic risk. 0: no risk factor presented (n = 162); 1–2: subjects with 1 or 2 risk factors (n = 162); 3–4: subjects presenting 3 or 4 risk factors (n = 87); F: females; M: males; BMI: body mass index; ICO: index of central obesity; SBP: systolic blood pressure; DBP: diastolic blood pressure; MAP: mean arterial pressure; PP: pulse pressure; FPG: fasting plasma glucose; FIns: fasting plasma insulin; QUICKI: quantitative insulin sensitivity check index; CHOL: total cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol; VLDL-C: very low density lipoprotein cholesterol; TAG: triacylglycerols; AIP: atherogenic index of plasma; eGFR: estimated glomerular filtration rate; Vitamin D₃: plasma 25(OH)D₃; PTH: intact parathormone; chi: chi-square</p><p>*: p<0.05 vs. cardiometabolic risk factors free subjects</p><p>**: p<0.01 vs. cardiometabolic risk factors free subjects</p><p>***: p<0.001 vs. cardiometabolic risk factors free subjects</p><p>+: p<0.05 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>++: p<0.01 vs. subjects presenting 1 or 2 cardiometabolic risk factors</p><p>+++: p<0.001 vs. subjects presenting 1 or 2 cardiometabolic risk factors; <i>italics</i>: statistical evaluation performed on logarithmically transformed data</p><p>Cohort characteristics: anthropometric data, blood pressure, standard blood chemistry variables and 25(OH)D₃ levels.</p

Effects of Trigonelline, an Alkaloid Present in Coffee, on Diabetes-Induced Disorders in the Rat Skeletal System

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