Effect of Parenteral Antioxidant Supplementation During the Dry Period on Postpartum Glucose Tolerance in Dairy Cows.

BACKGROUND: Exacerbated postparturient insulin resistance (IR) has been associated with several pathologic conditions in dairy cattle. Oxidative stress (OS) plays a causative role in IR in humans, and an association, but not direct relationship, between OS and IR recently has been reported in transition dairy cattle. HYPOTHESIS: Supplementation with antioxidants shortly before calving improves glucose tolerance after parturition in dairy cattle. ANIMALS: Ten late-pregnant Holstein cows entering their 2nd to 5th lactation. METHODS: Randomized placebo-controlled trial: 15 ± 2 days before expected calving, the treatment group received an injection of DL-alpha-tocopheryl acetate at a dosage of 6 mg/kg body weight (BW) and 0.06 mg/kg BW of sodium selenite, and the control group was injected with isotonic saline. During the first week after calving, both groups underwent glucose tolerance testing (0.25 g glucose/kg BW). Commercial assays were used to quantify the concentrations of glucose, insulin, nonesterified fatty acids (NEFA), beta-hydroxybutyrate, and markers of redox status in blood. Data were analyzed using the Mann-Whitney U-test (α = 0.05). RESULTS: Supplemented cows showed a lower risk for OS, as reflected by a lower OS index (P = .036), different areas under the curve for the concentrations of glucose (P < .01), insulin (P = .043), and NEFA (P = .041), more rapid elimination rates (P = .080, <.01 and .047 respectively), and shorter half-lives (P = .040, <.01 and .032) of these metabolites. CONCLUSIONS AND CLINICAL IMPORTANCE: Supplementation with antioxidants before calving resulted in greater insulin sensitivity after calving, thereby suggesting the role of OS in the development of IR in cattle and the potential benefits of antioxidant supplementation in minimizing the consequences of negative energy balance.

The importance of the oxidative status of dairy cattle in the periparturient period: revisiting antioxidant supplementation.

Dairy cows are especially vulnerable to health disorders during the transition period, when they shift from late pregnancy to the onset of lactation. Diseases at this stage affect not only the animals' well-being, but also cause a major economic impact in dairy farms, because apart from treatment costs, affected cows will not reach their peak milk-producing capacity. The overproduction of reactive oxygen species (ROS) leads to oxidative stress, which has been identified as an underlying factor of dysfunctional inflammatory responses. Supplementation with vitamins and trace elements attempts to minimize the harmful consequences of excessive ROS production, thereby trying to improve animals' health status and to reduce disease incidence. However, results regarding the effects of supplementing antioxidants on dairy cows' health and performance have been inconsistent, because in most cases, the antioxidant potential of the animals was not assessed beforehand and the nutritional strategy planned accordingly. Therefore, reviewing the physiological and harmful effects of ROS production, along with the different options available for assessing the redox balance in dairy cattle and some of the key findings of different supplementation trials, could bring one step forward the on-farm application of determinations of oxidative status for establishing nutritional strategies early enough in the dry period that could improve transition cow health.

Study of dissolution profiles and desintegration of capsules containing the dried hydroethanolic extract of Calophyllum brasiliense

Calophyllum brasiliense Cambess, Calophyllaceae, is of great interest in folk medicine and is used in the treatment of various diseases such as diabetes. Granules containing the hydroethanolic extract from the stem bark of C. brasiliense were obtained. The polyphenol content was standardized, and the average weight, disintegration, and the dissolution profiles of the capsules were determined after encapsulation. The capsules had an average weight of 574.5±8.0 mg. In vitro tests showed that the most efficient disintegration profile was in hydrochloric acid buffer (pH 1.2), with a capsule disintegration time within 9 min. The dissolution analysis showed a better uniformity of capsule content release when the test was performed in a hydrochloric acid buffer (pH 1.2), with a maximal release rate at 15 min (giving a polyphenol content of 4.38%, which corresponds to a concentration of 0.0080 mg/mL). In distilled water, the maximal release was reached at 20 min (giving a polyphenol content of 5.41%, which is equivalent to 0.0105 mg/mL). In phosphate buffer, the maximal release of capsule contents was reached at the end of the dissolution assay (30 min), with the lowest amount of released polyphenols (3.61%, which corresponds to a concentration of 0.0070 mg/mL). The encapsulated form of the hydroethanolic extract of C. brasiliense was shown to have the necessary traits of a desirable delivery agent, and the dissolution test was an effective analysis of this material's polyphenol release profile for the specific dosage form.

Histochemistry evaluation of the oxidative stress and the antioxidant status in Cu-supplemented cattle.

The aim of this paper is to evaluate at a histopathological level the effect of the most commonly used copper (Cu) supplementation (15 mg/kg dry matter (DM)) in the liver of intensively reared beef cattle. This was done by a histochemistry evaluation of (i) the antioxidant capacity in the liver - by the determination of metallothioneins (MT) and superoxide dismutase (SOD) expression - as well as (ii) the possible induction of oxidative damage - by the determination of inducible nitric oxide synthase (iNOS), nitrotyrosine (NITT), malondialdehyde (MDA) and 8-oxoguanine (8-oxo) - that (iii) could increase apoptotic cell death - determined by cytochrome-c (cyto-c), caspase 1 (casp1) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Liver samples from Cu-supplemented (15 mg Cu sulphate/kg DM, n = 5) and non-supplemented calves (n = 5) that form part of other experiments to evaluate Cu status were collected at slaughter and processed for immunohistochemistry and TUNEL. MT expression was diffuse and SOD showed slight changes although without statistical significance. iNOS and NITT positive (+) cells significantly increased, mainly around the central veins in the animals from the Cu-supplemented group, whereas no differences were appreciated for the rest of the oxidative stress and apoptosis markers. Under the conditions of this study, which are the conditions of the cattle raised in intensive systems in NW Spain and also many European countries, routinely Cu supplementation increased the risk of the animals to undergo subclinical Cu toxicity, with no significant changes in the Cu storage capacity and the antioxidant defensive system evaluated by MT and SOD expression, but with a significant and important increase of oxidative damage measured by iNOS and NITT. The results of this study indicated that iNOS and NITT could be used as early markers of initial pathological changes in the liver caused by Cu supplementation in cattle, although more studies in cattle under different levels of Cu supplementation are needed.

Effect of moderate Cu supplementation on serum metabolites, enzymes and redox state in feedlot calves.

The aim of this investigation was to evaluate whether, in the nutritional management of commercial feedlots, copper (Cu) supplementation is justified to maintain the physiological requirements. This study compared beef calves fed concentrates with an average Cu basal content of 5 and 8 mg/kg in growing and finishing periods (10 animals) or supplemented with 15 mg/kg for each phase (20 animals) as regards production indices, metabolic parameters [glucose, nonesterified fatty acids (NEFA), cholesterol, serum urea nitrogen (SUN), creatinine, total serum protein (TSP), albumin, aspartate transaminase (AST) and γ-glutamyl transferase (GGT)] and markers of oxidative stress (reactive oxygen species (ROS) and serum antioxidant capacity (SAC)). Data were recorded at ages 12, 24 and 36 weeks. In general, Cu supplementation was neither detrimental nor beneficial for animal health and performance, and the levels of the measured metabolites and enzymes were within their normal ranges stated for feedlot with the same management during the whole study. However, in keeping with reported higher hepatic Cu levels at slaughter, animals on supplemented feed had higher GGT activities at the end of the finishing stage, although the difference was not statistically significant. On the other hand, lower SAC levels at the end of the growing period in the supplemented group suggest the possibility of a positive effect of Cu supplementation on redox state. Further research is necessary to clarify the potential role of Cu in limiting the ROS production associated with fattening diets, and to evaluate the hepatobiliary consequences of supplementation, including hepatic Cu accumulation.

Influence of Cu supplementation on toxic and essential trace element status in intensive reared beef cattle.

The aim of this study is to evaluate if dietary Cu supplementation that leads to a hepatic Cu accumulation over the normal range has an influence on trace element status that could contribute to the pathogenesis of other mineral related disorders. Samples (liver, kidney, spleen, diaphragm and brain) of beef calves receiving typical commercial diets Cu supplemented and non-supplemented were tested for differences in non-essential and essential trace elements determined by ICP-MS. As (kidney and diaphragm), Hg (liver and kidney), and Pb (liver, kidney and spleen) were significantly lower, while Cd residues (liver and kidney) were significantly higher in the Cu supplemented group. Mn and Ni significantly decreased and Mo increased in the brain, and Se (diaphragm) decreased in the Cu supplemented group. These interactions are unknown, and possibly with more than two metals involved as suggested in the case of the ratio Se:Cu in the animals of this study. The possible role of Cu supplementation on the status of certain metals associated to neurological diseases (Mn-Ni) in the brain deserves further investigation. Finally new research on Cu-Se supplementation is necessary to better understand the risk of the animals to suffer from Se deficiency.

Effect of type of muscle and Cu supplementation on trace element concentrations in cattle meat.

Considering that meat is an important source of metals exposure to humans it is important to explore trace element concentrations in different types of muscles. Because of the demonstrated effect of Cu-supplementation on mineral status, the influence of Cu-supplementation was also evaluated. Samples of four different muscles (diaphragm, cardiac, semitendinous and pectoral, n=120) from beef calves receiving typical commercial diets Cu-supplemented (15 mg Cu(2)SO(4)/kg DM) and non-supplemented were taken and acid digested. The levels of non-essential (As, Cd, Hg, Pb and Sn) and essential (Co, Cr, Fe, Mn, Mo, Ni, Se and Zn) elements were analyzed by ICP-MS. The statistical analyzes included two way Anova, post hoc DHS Tukey and Spearman correlations. The most active and less fat containing muscles showed in general the highest essential and the lowest non-essential trace element accumulation. As and Hg muscular residues are indicative of animal exposure, however, in situations of an adequate mineral status, essential trace element concentrations in muscle are irrespective of the mineral status of the animal and could be possibly related to their own particular muscular metabolism. Cu-supplementation significantly reduced As but caused a significant decrease of Se, which could have significance for the animal's health.

The influence of reproductive stage on the selenium status of sheep in a low-selenium region.

The selenium status of sheep was evaluated during the reproductive stage in a region of low selenium level. Serum selenium concentration, whole blood glutathione peroxidase activity (GSH-Px), which is a good indicator of protection against oxidative damage, as well as the activities of creatine kinase (CK) and aspartate aminotransferase (AST), the plasma indicators of muscle damage, were evaluated in a group of ewes during gestation and lactation and in their lambs. The selenium requirements of ewes were found to increase during lactation. There were no differences in GSH-Px activity between the experimental and the control groups throughout the reproductive stage. In the second half of pregnancy GSH-Px activity was subnormal. In spite of this, no evidence of existing pathologic conditions associated with selenium deficiency was found, since the muscle markers CK and AST were within the normal range. In the same way, no distinct symptoms of nutritional myopathy were observed in the lambs, suggesting that the low selenium level found in the ewes did not cause alterations in their development.