Effect of nano-sized, elemental selenium supplement on the proteome of chicken liver.

The nano-sized (100-500 nm) selenium has higher bioavailability and relatively lower toxicity compared to other selenium forms. The objective of the present study was to compare liver proteome profiles of broiler chicken fed with control diet without Se supplementation and diet supplemented with nano-Se with 4.25 mg/kg DM. Differential proteome analyses were performed by two-dimensional gel electrophoresis (2D-PAGE) followed by tryptic digestion and protein identification by liquid chromatography-mass spectrometry (LC-MS). Seven hundred and eight spots were detected, and 18 protein spots showed significant difference in their intensity (p < 0.05) between the two groups. In response to nano-Se supplementation, the expression of 8 proteins was higher, and 5 proteins were lower in nano-Se supplemented group compared to control group. The functions of the differentially expressed proteins indicate that the high dose of selenium supplementation induced a dietary stress. Selenium supplementation may influence the metabolism of fatty acids and carbohydrates and antioxidant system, and increase the quantity of cytoskeletal actin and the expression of actin regulatory protein as well.

Phase I study of the botanical formulation PHY906 with capecitabine in advanced pancreatic and other gastrointestinal malignancies.

PURPOSE: The botanical formulation, PHY906, has been used widely in Eastern countries to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. PHY906 may also have anti-tumor properties and may potentiate the action of several chemotherapeutic agents based on pre-clinical studies. We conducted a Phase I study using PHY906 in combination with capecitabine in patients with advanced pancreatic and gastrointestinal malignancies to determine the maximum tolerated dose (MTD) of capecitabine in combination with PHY906. PATIENTS AND METHODS: This study was a single institution, open-label, Phase I study of PHY906 800mg BID on days 1-4 in combination with escalating doses of capecitabine (1000, 1250, 1500, and 1750mg/m(2)) orally twice daily on days 1-7 of a 14-day cycle (7/7 schedule). Capecitabine was increased until the appearance of dose limiting toxicities (DLTs). Measurements of efficacy included tumor response by Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Twenty-four patients with a median age of 67 years (range 40-84) with pancreatic cancer (15), colon cancer (6), cholangiocarcinoma (1), esophageal cancer (1) and unknown primary (1) received a total of 116 cycles (median 5 cycles; range 1-17 cycles) over 4 dose levels of capecitabine. One DLT (Grade 4 AST/ALT, Grade 3 hyponatremia) was observed in the 1000mg/m(2) cohort of patients. No further DLT was observed in the subsequent cohorts and doses of capecitabine were escalated to 1750mg/m(2) BID. There were no DLTs at the maximum dose level of 1750mg/m(2), however, the delivered dose-intensity of capecitabine was similar at the 1750mg/m(2) dose level as the 1500mg/m(2) dose level. Therefore, the MTD was defined at 1500mg/m(2) of capecitabine in this dosing schedule with PHY906. One patient achieved a partial response, and 13 patients had stable disease that lasted more than six weeks. CONCLUSION: The MTD of capecitabine was determined to be 1500mg/m(2) BID administered in a 7/7 schedule, in combination with PHY906 800mg BID on days 1-4. This combination was well tolerated and warrants further study.

Effect of dietary fatty acid pattern on growth, body fat composition and antioxidant parameters in broilers.

The effects of dietary fat supplementation on performance, fatty acid (FA) composition of tissues and antioxidant defence system of broilers were studied. Male broilers were placed in 20 floor pens (60 broilers per pen). The broilers were fed by diets with added different energy sources: lard (L); sunflower oil (SFO); soybean oil (SBO); and linseed oil (LSO). The treatments did not modify significantly growth performance and feed intake of the broilers. There was no effect of dietary FA pattern on reduced glutathione level and glutathione peroxidase activity of plasma, erythrocyte and liver samples. However, higher PUFA content of the diet resulted in a significant increase in malondialdehyde level of erythrocytes and liver. The broilers fed LSO diet more effectively maintained their antioxidant status with enhanced plasma radical scavenger capacity. FA composition in tissues reflected the FA pattern of the diets, although proportion of FAs with four or more double bonds was metabolic specific. LSO diet increased the level of C18:3, C20:5 and C22:6 in tissue lipids in relation to L, SFO and SBO diets. Significantly increased plasma radical scavenging capacity in concert with the enhanced C20:5 and C22:6 proportion in liver and muscle during LSO feeding indicate metabolic changes to counteract the oxidative injury. This may be related to the compounds produced after different biochemical pathways of n-6 and n-3 FAs.

Effects of oral L-carnitine, L-lysine administration and exercise on body composition and histological and biochemical parameters in pigeons.

The purpose of this study was to examine whether L-carnitine and its precursor L-lysine could have any beneficial effect in racing pigeons, and if so, whether this effect is influenced by the extent of exercise (short-distance flight: 135 km vs. long-distance flight: 580 km). Birds were divided into seven groups of animals. Group 1: negative control, no flight, no treatment, Group 2: positive control, placebo treatment before the short-distance flight, Group 3: 200 mg/day L-carnitine treatment before the short-distance flight, Group 4: 400 mg/day L-lysine treatment before the short-distance flight, Group 5: positive control, placebo treatment before the long-distance flight, Group 6: 200 mg/day L-carnitine treatment before the long-distance flight, Group 7: 400 mg/day L-lysine treatment before the long-distance flight. L-carnitine, L-lysine and distilled water (placebo) were orally administered (tube feeding) for 7 days before flight. Just after returning home, blood samples were collected and analyzed for glucose, fructosamine, cholesterol, triglycerides and thiobarbituric acid reactive substances. Pigeons were euthanized using carbon dioxide as an inhalation agent, and the whole body was subjected to proximate analysis. The status at arrival was referred to as a basis for comparison. Sex did not affect the measured parameters. As a result of the L-carnitine and L-lysine administrations, the body fat mobilization was higher during the 580 km flight, whereas no changes were noted during the 135 km flight. The main changes in the measured blood parameters were caused by the extent of exercise. This experiment considered the extent of exercise as a factor potentially modulating L-carnitine supplementation effects. In conclusion, flight distance affected several parameters but the supplements of L-carnitine and L-lysine were not effective in the tested situations.

Investigation of lipid peroxide and glutathione redox status of chicken concerning on high dietary selenium intake.

This study was designed to investigate the effects of excess (24.5 mg Se/kg feed) inorganic and organic dietary selenium supplementation on 3-week-old broilers. The experiments lasted 4 days. Intensity of lipid peroxidation processes (malondialdehyde, MDA) and the amount (reduced glutathione, GSH) and activity (glutathione peroxidase activity, GSHPx) of gluathione redox system were measured in blood plasma, red blood cell hemolysate and liver. Voluntary feed intake in the selenium-treated groups reduced remarkably. Elevated GSH concentration and GSHPx activity were measured in plasma and liver of both selenium-treated groups compared to the untreated control and the 'pair-fed' controls. The lipid peroxidation processes in the liver showed higher intensity than the control due to both selenium treatment. The applied dose of selenite and selenomethionine does not inhibit, but even improves the activity of glutathione redox system in the liver during the early period of selenium exposure.

Effect of feeding T-2 toxin contaminated feed on the utilisation of vitamin E in chickens.

The purpose of the present study was to investigate the effect of experimental T-2 toxin load (2.35 mg/kg of feed) and vitamin E supply in the drinking water (10.5 mg/bird/day) on vitamin E levels of the blood plasma and liver in broiler chickens in a 14-day experiment. It was found that T-2 toxin load did not influence vitamin E content of the blood plasma except at day 3 after the toxin load when a moderate increase was detected in plasma vitamin E. No significant changes were found in vitamin E content of the liver. The simultaneous use of high-dose vitamin E supplementation and T-2 toxin load caused a significantly higher plasma vitamin E content but the changes were less expressed in the group subjected to T-2 toxin load. Vitamin E supply also resulted in a marked and significant increase in vitamin E concentrations of the liver on days 3 and 7 even in the T-2 loaded group, but this concentration significantly decreased thereafter. The results show that T-2 contamination of the diet has an adverse effect on the utilisation of vitamin E in broiler chickens.

Effect of different dietary fat sources on production traits, lipid peroxide status and on the glutathione redox system in African catfish [Clarias gariepinus (Burchell)] fingerlings. Short communication.

Lipids are used to provide the energy to cover the metabolic needs and to provide essential fatty acids, which are important for membrane function [12]. Fats may contain high level of long chain polyunsaturated fatty acids, which are prone to peroxidation [8] and will interact with the antioxidant defense system [1]. There is contradiction in the literature about whether the intake of fish oil enhance [7] or deplete [4] tissue antioxidant defenses and the glutathione redox system in different organisms. The aim of the present study was to examine the effects of different dietary oils on parameters of the lipid peroxide state and the glutathione redox system in C. gariepinus fingerlings.

Effect of excess selenium supplementation on the glutathione redox system in broiler chicken.

Selenium, as part of selenocysteine, is the active centre of selenoenzymes. Excess amount of selenium generates oxygen free radicals and reacts with thiol compounds such as reduced glutathione, composing seleno-diglutathione. These reactions impair the amount and/or activity of the biological antioxidant defence system. In the present experiment the effects of two inorganic selenium sources (Na2SeO3, Na2SeO4) on lipid peroxidation and on the content and activity of some components of the antioxidant defence mechanism were studied in Ross 308 hybrid cockerels. In the tissues examined, the glutathione redox system was altered in different ways as an effect of excess selenium. The amount of glutathione and, consequently, glutathione peroxidase activity declined in the blood plasma and in the red blood cell haemolysate, while in the liver malondialdehyde concentration increased only at the end of the experimental period as a result of the boosted enzyme activity. The authors suppose that the cause of increased lipid peroxidation was the potential toxic effect of selenium accumulation above the actual demand.

Effect of supplementation with methionine and different fat sources on the glutathione redox system of growing chickens.

The effect of supplementary methionine and fats of different saturation levels on the glutathione redox system of growing broiler cockerels was studied. The diet of three groups of chicks was supplemented with corn germ oil, beef tallow and fish oil at the levels of 30 g/kg and 50 g/kg of feed, respectively. The diet of further three groups was supplemented with methionine (5 g/kg of feed) in addition to the different fat sources. Control chicks were fed with a compound feed without methionine and fat supplementation. Reduced glutathione (GSH) and glutathione disulphide (GSSG) content as well as glutathione peroxidase activity in the liver were determined and GSH/GSSG ratio was calculated at day old and then at one and three weeks of age. Our results indicate that supplementary methionine stimulates both the synthesis of the glutathione redox system and glutathione peroxidase activity in growing chickens in the first period of postnatal life, when the risk of lipid peroxidation is high due to feeding unsaturated fats in the diet.

Environmental induction models for the investigation of activity: changes in glutathione peroxidase, a crucial factor of the antioxidant defence.

Glutathione peroxidase enzyme superfamily plays significant role in the elimination of reactive oxygen free radicals in the animals. Many characteristics of these proteins have been revealed already, but their regulation is still not known. Several data suggest that some environmental factors have certain regulatory effect, while others propose strict genetic regulation. In this report we present four different environmental induction models in which New Zealand white rabbits were used as experimental animals. In three models, free radical load of different origin, lipidperoxide load, application of a glutathione depletor or a prooxidant agent, was introduced. Beside these negative models a positive model was also constructed in which additive selenium was supplied. Glutathione peroxidase activity was measured in blood serum, erythrocyte haemolysate and liver. Reduced glutathione, and malondialdehyde concentration in the liver were also determined. According to the results, the established models are capable for analysing the enzyme activity x environmental interactions.

Effects of phytase supplementation on calcium and phosphorus output, production traits and mechanical stability of the tibia in broiler chickens.

A feeding trial was performed using 4 x 60 day-old chickens (Ross 208 cockerels) raised up to 42 days of age to determine whether exogenous phytase addition increases phosphorus utilisation by broiler chickens, and to assess its effects on some production traits as well as on the ash content and mechanical stability of the tibia. The chickens' feed consisted of maize, wheat, soybean meal, fish meal, yeast, and fat powder. The basic feed was supplemented with inorganic phosphorus in groups A and B. In groups C and D, the amount of the inorganic phosphorus supplement (DCP) was decreased by 50%, at the same calcium/phosphorus ratio. The 50% reduction of inorganic phosphorus supplementation represents a 20% decrease of total phosphorus. To the diets of groups B and D a phytase enzyme preparation (Phytase Novo CT) was added. The calculated exogenous phytase activity was 600 FYT/kg feed. The decrease of inorganic phosphorus did not cause significant differences in the daily weight gain but lowered the feed conversion rate by 10%. Calcium and phosphorus excretion decreased by 18% and 15%, and the breaking strength of the tibia was also lower. Phytase supplementation of the feed at a lower rate of inorganic phosphorus supplementation did not cause changes in the body weight gain but improved the feed conversion rate by 5.6%. Phosphorus and calcium output decreased by 21% and 11%, respectively, but chemical composition and mechanical stability of the tibia were unaltered.

Nutritional metabolic diseases of poultry and disorders of the biological antioxidant defence system.

Deficiencies or disturbances of nutrition cause a variety of diseases and can arise in different ways. The amount of a particular nutrient in the diet may be insufficient to meet the requirements, the diet may contain substances that inactivate the nutrient or inhibit its absorption/utilisation, or metabolism may be upset by the interaction of dietary and environmental factors. Peroxidation of lipids or oxygen free radical generation in general is a physiological process important for cell metabolism, division and differentiation and also for the biosynthesis of hormones and prostaglandins. Free radicals generated through these processes are effectively scavenged by the antioxidant defence system. Uncontrolled lipid oxidation caused by disturbances of that system may play a crucial role in some important poultry diseases and toxicoses. The first route of lipid peroxide loading of the organism is via the feed, such as through oxidised lipids. Oxidised fatty acids are absorbed from the intestine mainly in the form of unsaturated keto compounds and initiate lipid peroxidation in the tissues. The second problem is the insufficient amount of antioxidants in the feed, e.g. vitamin E deficiency. Nutritional encephalomalacia is a problem in poultry production which depends both on the actual vitamin E supply and the dietary amount of polyunsaturated fatty acids. In young birds the primary target of vitamin E deficiency is the brain because it contains low amounts of vitamin E, and the vitamin E content of the liver acting as store decreases rapidly during the first week of life. Besides vitamin E, other components of the antioxidant system, e.g. the antioxidant enzymes (catalase and glutathione peroxidase) also have low activity in the brain as compared to other major tissues. The brain is highly susceptible to oxidative stress because of the accumulation of polyunsaturated fatty acids. The third source of free radical generation is the toxic level of different feed ingredients, e.g. toxicoses caused by vitamin A, selenium, and ionophore antibiotics. Other important aspects of antioxidants (e.g. vitamin E and selenium) in poultry are stimulation of the immune response (e.g. in the case of vaccination) and reduction of the risks of free radical formation as a result of macrophage function.

Effect of vitamins A and E on blood plasma vitamin status and daily body mass gain of different fat-tailed sheep breeds.

Ninety ram lambs of three Iranian fat-tailed sheep breeds including the Shal breed (age: 4-6 months) in one experiment and the Sanjabi and Bakhtiari breeds (6-9 months) in another experiment were assigned to five groups of 5-7 lambs each to receive a basal diet plus different levels of vitamins A and E supplementation. The groups received 0, 50 or 100 IU vitamin A/kg body mass (b.m.) and 0, 15 or 30 IU vitamin E/kg of diet. In the vitamin A groups a constant level of 15 IU vitamin E and in the vitamin E groups a constant level of 50 IU vitamin A supplementation was provided. Blood plasma samples were taken at the beginning and at the end of the experiments and the concentrations of vitamins A and E were determined by high-performance liquid chromatography (HPLC). Vitamin A supplementation of the highest level (100 IU/kg b.m.) significantly increased the retinol content of the blood plasma in the Shal (P < 0.01) and Bakhtiari (P < 0.05) breeds. The mild increase of retinol concentration in the Sanjabi breed was not significant (P > 0.05). Vitamin A supplementation greatly decreased the alpha-tocopherol content of the blood plasma in all three breeds (P < 0.01). It increased the average daily body mass gain of lambs of the Shal breed (P < 0.01) but decreased that of Bakhtiari lambs (P < 0.05). Supplementation of vitamin E mildly decreased the retinol content of the blood plasma in all the breeds and the decrease was statistically significant (P < 0.05) for the Shal breed at the highest dose level. Vitamin E supplementation greatly increased the alpha-tocopherol concentration of the blood plasma in all the breeds (P < 0.01-0.001). It decreased the average daily body mass gain of the Shal breed (P < 0.001) but improved it in the two other breeds. That increase was statistically significant (P < 0.05) in the Bakhtiari breed. It was concluded that the Shal breed gave a better response to vitamin A supplementation while the Sanjabi and Bakhtiari breeds to vitamin E. This indicates that fat-tailed breeds have dissimilar requirements for vitamins A and E supplementation. A higher level of vitamin E intake is required for raising the alpha-tocopherol content of the blood plasma above the level critical for sheep (0.8 microgram/ml).

Seasonal variation in the concentration of vitamins A and E in the blood plasma of fat-tailed sheep.

Six non-pregnant ewes and 6 rams (age: 3-4 years) of an Iranian fat-tailed sheep breed (Shal) were used. Blood samples were collected monthly for 12 months, and the concentrations of retinol and alpha-tocopherol were determined by high-performance liquid chromatography (HPLC). A limited ration of standard composition was fed throughout the year. The ration was supplemented with 25-32 IU alpha-tocopherol/animal/day. Vitamin A concentrations in the blood plasma of ewes were lower in the spring (442 +/- 9 micrograms/L) and summer (452 +/- 7 micrograms/L) and higher in the autumn (467 +/- 5 micrograms/L). In the rams, the plasma concentration of vitamin A was the lowest in the spring (436 +/- 6 micrograms/L) and the highest in the summer (471 +/- 5 micrograms/L). A seasonal comparison did not show statistical differences between consecutive seasons for the ewes (P > 0.05). The differences were significant between winter and spring (P < 0.05) and spring and summer (P < 0.001) for the rams. The blood plasma concentration of vitamin E was 1.21 +/- 0.05, 1.04 +/- 0.05, 1.24 +/- 0.05 and 1.24 +/- 0.08, mg/L in spring, summer, autumn and winter, respectively, for the ewes and 1.24 +/- 0.05, 1.11 +/- 0.06, 1.09 +/- 0.04 and 1.38 +/- 0.07 mg/L in spring, summer, autumn and winter, respectively, for the rams. The values were significantly different between spring and summer (P < 0.05) and summer and autumn (P < 0.01) for the ewes. In rams, the values obtained in autumn also showed a significant difference (P < 0.001) from those found in winter. Differences between values found in other seasons were not significant (P > 0.05). The retinol and alpha-tocopherol concentrations of the blood plasma were highly similar in the two sexes. The concentrations of retinol in the summer (P < 0.01) and alpha-tocopherol in the autumn (P < 0.05) showed significant differences between the two sexes. The results show that the concentrations of vitamins A and E are relatively constant in the blood plasma of fat-tailed sheep kept on a standardised feed. However, some differences due to the influence of season and sex were observed.

Effect of acute selenium toxicosis on the lipid peroxide status and the glutathione system of broiler chickens.

The effect of acute oral selenium toxicosis on the rate of lipid peroxidation, on the amount of reduced glutathione as well as on glutathione-peroxidase activity of the blood (plasma and red blood cells) and liver was studied in broiler chicken. Cockerels (28-day-old) were treated with selenium (4.85 mg/kg b.w.) administered intraoesophageally in the form of sodium selenite. Samples were at the onset of clinical signs (3 h after treatment) and 2 and 4 h thereafter. The malondialdehyde content of the blood plasma rose significantly (P < 0.05) at the onset of clinical symptoms but decreased later. Malondialdehyde content of the liver was higher than the control value at the first sampling (P < 0.01) and steadily increased later. Reduced glutathione content did not change significantly in the blood plasma and liver. Glutathione peroxidase activity of the RBC was significantly elevated (P < 0.01) only at the first sampling (3 h after treatment) and decreased to the control level thereafter. Acute oral selenium toxicosis increases the rate of lipid peroxidation in a short period of time (7 h) without exerting a significant effect on the glutathione system.

Blood glutathione peroxidase enzyme activity as an index of selenium release from Permasel in ewes.

Ten Merino ewes were given a single Permasel pellet (containing 5% of elementary selenium) orally and examined for the release of selenium in the reticulum by determining glutathione enzyme activity of the whole blood haemolysate over a period of 12 months. As compared to the controls, the treated ewes exhibited a significant elevation in glutathione peroxidase activity for 8 months, indicating an acceptable persistence of the product tested.

Effect of bulk feeds (alfalfa hay, corn silage) on the metabolism and liver parameters of growing geese.

Rearing experiments were conducted with a total of 90 liver hybrid geese from Babat, divided into three groups of 30 birds each. The effect exerted by all-concentrate feeding (group 1), concentrate feeding supplemented with alfalfa hay (group 2) or with corn silage (group 3) ad libitum on the blood glucose level, blood plasma total lipid, total cholesterol and free fatty acid level, and on total lipid content of the liver was studied. In addition, aspartate aminotransferase (AST) activity of the blood plasma and carotene, vitamin A and vitamin E concentration of the blood plasma and the liver were determined. It was found that the blood and liver parameters of goose groups fed different diets changed within the physiological limits typical of the species. Excessive fibre intake resulted in reduced lipid transport within the organism at an unchanged plasma cholesterol level; at the same time, blood glucose level remained unchanged. Ad libitum feeding of alfalfa hay and corn silage enhanced carotene and vitamin A transport and carotene storage but did not affect the transport of vitamin E. The results confirm earlier data of the literature that beta-carotene and vitamin A together impair vitamin E metabolism.