Tolerance of ruminant animals to high dose in-feed administration of a selenium-enriched yeast

The objective of the study was to determine if there were adverse effects on animal health and performance when a range of ruminant animals species were fed at least 10 times the maximum permitted European Union (EU) selenium (Se) dietary inclusion rate (0.568 mg Se/kg DM) in the form of selenium enriched yeast (SY) derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060. In a series of studies, dairy cows, beef cattle, calves and lambs were offered either a control diet which contained no Se supplement or a treatment diet which contained the same basal feed ingredients plus a SY supplement which increased total dietary Se from 0.15 to 6.25, 0.20 to 6.74, 0.15 to 5.86 and 0.14 to 6.63 mg Se/kg DM, respectively. The inclusion of the SY supplement (P < 0.001) increased whole blood Se concentrations, reaching maximum mean values of 716, 1,505, 1,377, and 724 ng Se/mL for dairy cattle, beef cattle, calves and lambs, respectively. Selenomethionine accounted for 10% of total whole blood Se in control animals whereas the proportion in SY animals ranged between 40 and 75%. Glutathione peroxidase (EC 1.11.1.9) activity was higher (P < 0.05) in SY animals when compared with controls. A range of other biochemical and hematological parameters were assessed, but few differences of biological significance were established between treatments groups. There were no differences between treatment groups within each species with regard to animal physical performance or overall animal health. It was concluded that there were no adverse effects on animal health, performance and voluntary feed intake to the administration of at least ten times the EU maximum, or approximately twenty times the US FDA permitted concentration of dietary Se in the form of SY derived from a specific strain of Saccharomyces cerevisiae CNCM I-3060.

Effect of acute administration of recombinant human leptin during the neonatal period on body temperature and endocrine profile of the piglet

Background: Leptin is produced predominantly by white adipocytes; in adults it regulates appetite and energy expenditure but its role in the neonate remains to be fully established. Objectives: To examine the effects of acute administration of recombinant human leptin on the endocrine profile and thermoregulation of neonatal pigs. Methods: 24 pairs of siblings (n = 48) were administered with either a single dose (4 mu g ml(-1) kg(-1) body weight) of leptin (L: n = 24) or a placebo (P: n = 24) on day 6 of neonatal life. Rectal temperature was recorded, and tissue samples were taken at 1 (n = 12), 2 (n = 12), 4 (n = 12) or 6 (n = 12) hours post-administration. Plasma concentrations of hormones and metabolites were determined in conjunction with messenger RNA (mRNA) for leptin and uncoupling protein-2. Results: Plasma leptin increased following leptin administration, and differences in concentrations of insulin, thyroxine and non-esterified fatty acids were observed between the two groups. Initially, rectal temperature decreased in L pigs but returned to start values by 1.5 h. This decline in rectal temperature was delayed in placebo animals, resulting in differences between treatments at 1.5 and 2 h. Conclusions: Acute leptin administration alters the endocrine profile of pigs and influences the thermoregulatory ability of the neonate. Copyright (C) 2007 S. Karger AG, Basel.

Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats

Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15 nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18 % after 2 h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1.2 % only 18 h post-gavage, with the urine and faecal content constituting almost 90 % of the total recovered pelargonidin.

Distribution of [H-3]trans-resveratrol in rat tissues following oral administration

Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo. Here we investigated the distribution of metabolic products of [H-3]trans-resveratrol, following gastric administration. At 2 h, plasma concentrations reached 1 center dot 7 % of the administered dose, whilst liver and kidney concentrations achieved 1 center dot 0 and 0 center dot 6 %, respectively. Concentrations detected at 18 h were lower, being only 0 center dot 5 % in plasma and a total of 0 center dot 35 % in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25 %, respectively, of concentrations at 2 h, the brain retained 43 % of that measured at 2 h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7 mu m in plasma at 2 h. However, at 18 h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.

Maternal adipose tissue response to nicotine administration in the pregnant rat: effects on fetal body fat and cellularity

1. Nicotine has been implicated as a causative factor in the intrauterine growth retardation associated with smoking in pregnancy. A study was set up to ascertain the effect of nicotine on fetal growth and whether this could be related to the actions of this drug on maternal adipose tissue metabolism. 2. Sprague-Dawley rats were mated and assigned to control and nicotine groups, the latter receiving nicotine in the drinking-water throughout pregnancy. Animals were weighed at regular intervals and killed on day 20 of pregnancy. Rates of maternal adipose tissue lipolysis and lipogenesis were measured. Fetal and placental weights were recorded and analysis of fetal body water, fat, protein and DNA carried out. 3. Weight gains of mothers in the nicotine group were less in the 1st and 2nd weeks of pregnancy, but similar to controls in the 3rd week. Fetal body-weights, DNA, protein and percentage water contents were similar in both groups. Mean fetal body fat (g/kg) was significantly higher in the nicotine group (96.2 (SE 5.1)) compared with controls (72.0 (SE 2.9)). Rates of maternal lipolysis were also higher in the nicotine group. 4. The cause of these differences and their effects on maternal and fetal well-being is discussed.

Layer-by-layer coating of alginate matrices with chitosan–alginate for the improved survival and targeted delivery of probiotic bacteria after oral administration

The oral administration of probiotic bacteria has shown potential in clinical trials for the alleviation of specific disorders of the gastrointestinal tract. However, cells must be alive in order to exert these benefits. The low pH of the stomach can greatly reduce the number of viable microorganisms that reach the intestine, thereby reducing the efficacy of the administration. Herein, a model probiotic, Bifidobacterium breve, has been encapsulated into an alginate matrix before coating in multilayers of alternating alginate and chitosan. The intention of this formulation was to improve the survival of B. breve during exposure to low pH and to target the delivery of the cells to the intestine. The material properties were first characterized before in vitro testing. Biacore™ experiments allowed for the polymer interactions to be confirmed; additionally, the stability of these multilayers to buffers simulating the pH of the gastrointestinal tract was demonstrated. Texture analysis was used to monitor changes in the gel strength during preparation, showing a weakening of the matrices during coating as a result of calcium ion sequestration. The build-up of multilayers was confirmed by confocal laser-scanning microscopy, which also showed the increase in the thickness of coat over time. During exposure to in vitro gastric conditions, an increase in viability from <3 log(CFU) per mL, seen in free cells, up to a maximum of 8.84 ± 0.17 log(CFU) per mL was noted in a 3-layer coated matrix. Multilayer-coated alginate matrices also showed a targeting of delivery to the intestine, with a gradual release of their loads over 240 min.

Probiotic administration attenuates myocardial hypertrophy and heart failure following myocardial infarction in the rat

Background—Probiotics are extensively used to promote gastrointestinal health and emerging evidence suggests that their beneficial properties can extend beyond the local environment of the gut. Here, we determined whether oral probiotic administration can alter the progression of post-infarction heart failure. Methods and Results—Rats were subjected to six weeks of sustained coronary artery occlusion and administered the probiotic Lactobacillus rhamnosus GR-1 or placebo in the drinking water ad libitum. Culture and 16s rRNA sequencing showed no evidence of GR-1 colonization or a significant shift in the composition of the cecal microbiome. However, animals administered GR-1 exhibited a significant attenuation of left ventricular hypertrophy based on tissue weight assessment as well as gene expression of atrial natriuretic peptide. Moreover, these animals demonstrated improved hemodynamic parameters reflecting both improved systolic and diastolic left ventricular function. Serial echocardiography revealed significantly improved left ventricular parameters throughout the six week follow-up period including a marked preservation of left ventricular ejection fraction as well as fractional shortening. Beneficial effects of GR-1 were still evident in those animals in which GR-1 was withdrawn at four weeks suggesting persistence of the GR-1 effects following cessation of therapy. Investigation of mechanisms showed a significant increase in the leptin to adiponectin plasma concentration ratio in rats subjected to coronary ligation which was abrogated by GR-1. Metabonomic analysis showed differences between sham control and coronary artery ligated hearts particularly with respect to preservation of myocardial taurine levels. Conclusions—The study suggests that probiotics offer promise as a potential therapy for the attenuation of heart failure.

Activation of the G-protein coupled receptor 30 (GPR30) has different effects on anxiety in male and female mice

The GPR30, a former orphan GPCR, is a putative membrane estrogen receptor that can activate rapid signaling pathways such as extracellular regulated kinase (ERK) in a variety of cells and may contribute to estrogen's effects in the central nervous system. The distribution of GPR30 in the limbic system predicts a role for this receptor in the regulation of learning and memory and anxiety by estrogens. Though acute G-1 treatment is reported to be anxiogenic in ovariectomised female mice and in gonadally intact male mice, the effect of GPR30 activation is unknown in gonadectomised male mice. In this study, we show that an acute administration of G-1 to gonadectomised male mice, but not female mice, was anxiolytic on an elevated plus maze task, without affecting locomotor activity. In addition, though G-1 treatment did not regulate ERK, it was associated with increased estrogen receptor (ER)alpha phosphorylation in the ventral, but not dorsal, hippocampus of males. In the female, G-1 increased the ERK activation solely in the dorsal hippocampus, independent of state anxiety. This is the first study to report an anxiolytic effect of GPR30 activation in male mice, in a rapid time frame that is commensurate with non-genomic signaling by estrogen.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the alpha or beta isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1mug) of estradiol 48h and 24h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25mug) 48h and 24h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol.