Accelerated tissue aging and increased oxidative stress in broiler chickens fed allopurinol

Uric acid has been hypothesized as being one of the more important antioxidants in limiting the accumulation of glycosylated endproducts in birds. Study 1 was designed to quantitatively manipulate the plasma concentrations of uric acid using hemin and allopurinol while study 2 determined their effects on skin pentosidine, the shear force value of Pectoralismajor muscle, plasma glucose, body weight and chemiluminescence monitored oxidative stress in broiler chickens. Hemin was hypothesized to raise uric acid concentrations thereby lowering oxidative stress whereas allopurinol was hypothesized to lower uric acid concentrations and raise measures of oxidative stress. In study 1 feeding allopurinol (10 mg/kg body weight) to 8-week-old broiler chicks (n=50) for 10 days decreased plasma uric acid by 57%. However, hemin (10 mg/kg body weight) increased uric acid concentrations 20%. In study 2, 12-week-old broiler chicks (n=90) were randomly assigned to either an ad libitum (AL) diet or a diet restricted (DR) group. Each group was further divided into three treatments (control, allopurinol or hemin fed). Unexpectedly, hemin did not significantly effect uric acid concentrations but increased (P<0.05) measures of chemiluminescence dependent oxidative stress in both the DR and AL birds probably due to the ability of iron to generate oxygen radicals. Allopurinol lowered concentrations of uric acid and increased (P<0.05) the oxidative stress in the AL birds at week 22, reduced (P<0.05) body weight in both the AL and DR fed birds at 16 and 22 weeks of age, and markedly increased (P<0.001) shear force values of the pectoralismajor muscle. Skin pentosidine levels increased (P<0.05) in AL birds fed allopurinol or hemin fed birds, but not in the diet restricted birds at 22 weeks. The significance of these studies is that concentrations of plasma uric acid can be related to measures of oxidative stress, which can be linked to tissue aging.     

Gender-dependent impacts of body mass index and moderate alcohol consumption on serum uric acid—an index of oxidant stress status?

Uric acid seems to be causally involved in a variety of medical disorders involving oxidative stress. Although alcohol abuse and obesity are known to increase serum uric acid, the interactions between moderate drinking, adiposity, and uric acid metabolism have remained poorly understood. We examined serum uric acid concentrations from 2062 apparently healthy volunteers (970 men, 1092 women) reporting either no alcohol (abstainers) or < 40 g of ethanol consumption per day (moderate drinkers). The study population was further classified according to BMI as follows: < 19 (underweight), 19–25 (normal weight), 25–30 (overweight), and > 30 (obese). Serum uric acid concentrations in male moderate drinkers were significantly higher, and in females they were lower, than in the corresponding groups of abstainers. In the BMI-based subgroups, the highest concentrations were found in those who were overweight or obese. Significant two-factor interactions occurred between gender and drinking status (p < 0.001) and between gender and BMI (p < 0.02). Serum uric acid also correlated with indices of hepatocellular health (GGT, ALT, AST). The data indicate distinct gender-dependent impacts of alcohol consumption and BMI on serum uric acid. These findings should be applicable to the assessment of oxidative stress status and associated morbidity in alcohol consumers and individuals with excess body weight.     

Effect of ATP and Bax on the apoptosis of <Emphasis Type="Italic">Eimeria tenella</Emphasis> host cells

Background

Eimeria tenella (E. tenella) is a species of Eimeria that causes haemorrhagic caecal coccidiosis, resulting in major economic losses in the global poultry industry. After E. tenella infection, the amount of ATP and Bax in host cells showed highly significant changes. Therefore, it is necessary to investigate the effects of ATP and Bax on the apoptosis of E. tenella host cells.

Results

The ATP-treated group and the V5-treated group had higher E. tenella infection rates than the untreated group at 24, 48, 72, 96, and 120 h after infection with E. tenella. The results of flow cytometry showed that compared with the control group, the mitochondrial permeability transition pore (MPTP) opening in the untreated group was highly significantly increased (P?<?0.01) at 4, 24, 48, 72, 96, and 120 h. Moreover, results from Hoechst-Annexin V-PI staining and flow cytometry showed that the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those of the control group at 4 h, while the rates of early apoptosis, late apoptosis, and necrosis in the untreated group were higher at varying degrees than those in the control group at 24–120 h (P?<?0.05 or P?<?0.01). After treatment with ATP and Bax inhibitors, the rates of early apoptosis, late apoptosis, and necrosis, in addition to the MPTP opening in both the ATP-treated and V5-treated groups, were significantly lower (P?<?0.05) or highly significantly lower (P?<?0.01) than those in the untreated group.

Conclusions

ATP and Bax play important roles in regulating the apoptosis of E. tenella host cells.

     

The Effect of Enriched Milk with Selenium and Vitamin E on Growth Rate, Hematology, Some Blood Biochemical Factors, and Immunoglobulins of Newborn Goat Kids

Thirty male and female (n?=?15 for each one) Markhoz newborn goat kids (aged 7?±?3 days) were distributed in a randomized block design in a 2?×?2?+?1 factorial arrangement: two levels of sodium selenite as a source of selenium (0.2 or 0.3 ppm Se), two levels of α-tocopherol acetate as a source of vitamin E (150 or 200 IU Vit E), and one control treatment with six repetitions per treatment (each replicate included three male and three female kids). Animals were fed daily by Se-Vit E-enriched milk (Se-Vit E treatments) or non-enriched milk (control treatment). Growth rate, hematology, and serum biological parameters were measured. The levels of serum albumin (P?<?0.01), serum globulin (P?<?0.05), total serum protein levels (P?<?0.01), erythrocyte counts (RBC) (P?<?0.001), hemoglobin (P?<?0.001), hematocrit (P?<?0.001), leukocyte counts (WBC) (P?<?0.001), IgA (P?<?0.05), IgG (P?<?0.01), and IgM (P?<?0.01) significantly differed among treatments, while no significant differences were observed for calcium, lymphocyte, neutrophil average daily gain and body weight among treatments. Kids feeding by enriched milk with 0.3 ppm Se and 200 IU Vit E had significantly higher serum total protein, globulin, RBC, IgA, IgG, and IgM compared to control and those fed by enriched milk to 0.2 ppm Se and 200 IU Vit E had significantly higher WBC counts.     

Hyperuricemia Causes Pancreatic β-Cell Death and Dysfunction through NF-κB Signaling Pathway

Accumulating clinical evidence suggests that hyperuricemia is associated with an increased risk of type 2 diabetes. However, it is still unclear whether elevated levels of uric acid can cause direct injury of pancreatic β-cells. In this study, we examined the effects of uric acid on β-cell viability and function. Uric acid solution or normal saline was administered intraperitoneally to mice daily for 4 weeks. Uric acid-treated mice exhibited significantly impaired glucose tolerance and lower insulin levels in response to glucose challenge than did control mice. However, there were no significant differences in insulin sensitivity between the two groups. In comparison to the islets in control mice, the islets in the uric acid–treated mice were markedly smaller in size and contained less insulin. Treatment of β-cells in vitro with uric acid activated the NF-κB signaling pathway through IκBα phosphorylation, resulting in upregulated inducible nitric oxide synthase (iNOS) expression and excessive nitric oxide (NO) production. Uric acid treatment also increased apoptosis and downregulated Bcl-2 expression in Min6 cells. In addition, a reduction in insulin secretion under glucose challenge was observed in the uric acid–treated mouse islets. These deleterious effects of uric acid on pancreatic β-cells were attenuated by benzbromarone, an inhibitor of uric acid transporters, NOS inhibitor L-NMMA, and Bay 11–7082, an NF-κB inhibitor. Further investigation indicated that uric acid suppressed levels of MafA protein through enhancing its degradation. Collectively, our data suggested that an elevated level of uric acid causes β-cell injury via the NF-κB-iNOS-NO signaling axis.     

Effects of High Zinc Levels on the Lipid Synthesis in Rat Hepatocytes

Zinc deficiency impairs the hepatic lipid metabolism. Previous studies were focused on the negative effects of zinc deficiency on the hepatic lipid metabolism. A few studies investigated the effects of high zinc levels on the lipid metabolism in hepatocytes. In this study, rat hepatocytes were cultured and treated with different and high concentrations of zinc to investigate the effects of high zinc levels on the lipid synthesis in hepatocytes in vitro. The levels of hepatocytes functional markers, including alkaline phosphatase, lactate dehydrogenase, and albumin, were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). The mRNA and protein levels of sterol regulatory element-binding protein 1c (SREBP-1c) were significantly higher in the zinc treatment groups than in the control group (p?<?0.05, p?<?0.01). Furthermore, the mRNA expression levels of acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS) were significantly higher in the medium- and high-dose zinc treatment groups than in the control group (p?<?0.01). The mRNA levels of stearoyl-CoA desaturase-1 (SCD-1) were significantly higher in the high-dose group (p?<?0.01). These results indicate that high levels of zinc increase hepatocytes activity and SREBP-1c expression, which upregulate the expression of ACC1, FAS, and SCD-1, thereby improving the lipid metabolism in the hepatocytes.     

Effects of Selenium Supplementation on Expression of Endothelin-1 and Its Receptors in Pulmonary Microvascular Endothelial Cells from Chick Embryos

The objective of this study was to evaluate the effects of supplemental selenium (Se) on expression of endothelin-1 (ET-1) and its receptors in cultured chick embryos pulmonary microvascular endothelial cells (PMVECs). To accomplish this, PMVECs were treated in Se-deficient or Se-supplement (12, 24, 50, 100?ng/ml) culture medium for 48?h. Low Se medium was achieved by reducing serum concentrations and the essential growth factors were added. After the incubation, the effects of supplemental Se on ET-1 and its receptors gene expression were assessed by quantitative real-time PCR (qRT-PCR). Compared with the control group, our results showed that among the different concentrations of Se supplement, the levels of ET-1 gene expression treated with both the moderate Se doses (24, 50?ng/ml, P?<?0.01, P?<?0.01, respectively) and the high doses (100?ng/ml, P?<?0.05) were noticeably decreased, the low-dose group (12?ng/ml), which showed no changes. Meanwhile, Se supplement (24, 50, 100?ng/ml) was found to be effective in reducing the expression levels of ETA (P?<?0.01, P?<?0.05, P?<?0.05, respectively) in cultured PMVECs grown in low Se medium. However, there were no significant changes (P?>?0.05) in ETB mRNA levels during the cell proliferation. These observations indicated that Se may play both direct and indirect role in the regulation of ET-1 and its receptors gene expression and their production in avian PMVECs. Se supplement decreases in ET-1 and ETA production in Se-deficient PMVECs may partly explain the mechanism of the protective effects of the Se on the cardiovascular system.     

A zebrafish (danio rerio) model for high-throughput screening food and drugs with uric acid-lowering activity

With co-treatment of potassium oxonate (PO) and xanthine sodium salt (XSS), a zebrafish larva model of acute hyperuricemia has been constructed for the first time. The results show PO 200 μM + XSS 10 μM, PO 300 μM + XSS 15 μM, and PO 400 μM + XSS 20 μM can significantly increase the level of uric acid in the zebrafish larvae (P?<?0.05), the concentrations as described above can be used to construct the zebrafish larvae model of acute hyperuricemia. At the same time, treatment of allopurinol (APL, one of the hyperuricemia drugs) at 2000?μM?(P?<?0.001) and treatment of anserine (ASE) at 200?μM?(P < 0.05) could significantly decrease the level of uric acid in the model group which received PO 200 μM + XSS 10 μM, which demonstrate that such model could offer a new robust approach for high-throughput screening of food and drugs with uric acid-lowering activity.     

硝苯地平联合缬沙坦治疗老年原发性高血压疗效分析

目的:探讨硝苯地平缓释片联合缬沙坦治疗老年原发性高血压的临床疗效。方法:将180例患者随机分入对照组与观察组,给予对照组86例患者硝苯地平缓释片口服降压;观察组94例患者接受硝苯地平缓释片联合缬沙坦治疗,比较两组患者治疗8周后血压、心率、脉压、肾功、尿酸、血钾及尿微量白蛋白的变化。结果:治疗后观察组患者收缩压、舒张压、脉压及心率均显著降低,治疗总有效率高于对照组,两组比较差异有统计学意义(P<0.01);观察组尿酸、尿微量白蛋白显著优于对照组(P<0.01),两组肾功、血钾比较差异无统计学意义(P>0.05)。结论:硝苯地平缓释片联合缬沙坦治疗老年原发性高血压,降压平稳,同时可显著降低尿酸及尿微量白蛋白,改善肾功能。     

Protective Effects of Gallium, Germanium, and Strontium Against Ovariectomized Osteoporosis in Rats

The effects of trace elements of gallium (Ga), germanium (Ge), and strontium (Sr) on ovariectomized (OVX) osteopenic rats were studied in this paper. The urine calcium content, serum calcium, and phosphorus contents, bone mineral content, mineral dissolution, and mechanical strength of the osteopenic rats were analyzed respectively. After the rats were fed with Ga, Ge, and Sr diet for 8 weeks, respectively, the urine calcium content decreased (P?<?0.01). Plasma calcium and phosphate concentrations decreased in the order of OVX group?>?Ge group?>?Sr group?>?Ga group?>?Sham group. Mineral content increased in the order of OVX group?<?Ge group?<?Sr group?<?Ga group?<?Sham group. A dramatic decrease in calcium solubility was found both in the gallium and strontium treated animals (P?<?0.05). However, the same result did not occur in germanium treated groups. The data provide an important proof of concept that gallium and strontium might be a new potential therapy for the management of postmenopausal osteoporosis in humans.     

Effect of 3:7 ratio of Astragalus total saponins and Curcumin on the diabetic nephropathy rats model

Objective

Study the effect of the 3:7 ratio of Astragalus total saponins and Curcumin on the model of diabetic nephropathy rats, and explore its mechanisms.

Mechanism of protection against arachidonate induced sudden death by glucocorticoid

Dexamethasone at a dose of 6 mg^?kg^?1 given to rabbits for three days prior to challenge with sodium arachidonate (2 mg^?kg^?1) intravenously, improved survival from 0% to 90% (p<0.01). Dexamethasone, given for shorter periods prior to arachidonate injection resulted in survival rates from 17% to 40%. In dexamethasone (3 days) treated rabbits, plasma thromboxane B₂ concentrations were only increased by 30% compared with increases of 950% in untreated rabbits (p<0.001). Dexamethasone treated rabbits did not exhibit pulmonary thrombosis as did untreated rabbits given arachidonate. However, platelet rich plasma from both control and treated rabbits was aggregated by 0.2 mM arachidonate $\text{in vitro}$. The mechanism of the protective effect of dexamethasone appears to be related to induction of enzymes or stimulation of clearance of injected arachidonic acid, since steroid treated rabbits cleared labeled arachidonic acid more rapidly than untreated rabbits.     

A novel SNP of liver-type fatty acid-binding protein gene in duck and its associations with the intramuscular fat

Liver-type fatty acid-binding protein (L-FABP) is a member of intracellular lipid-binding proteins involved in the transportation of fatty acids. We detected the polymorphisms of duck L-FABP gene and its association with the intramuscular fat (IMF) and other fat-related traits. The complete sequence of duck L-FABP gene (four exons and three introns, 2,542?bp) was obtained in this study. The polymorphism of L-FABP gene was examined with direct DNA sequencing method in 231 individuals from different breeds, and a novel single nucleotide polymorphism in the exon 3 was detected. The polymorphism was shown to be associated with the contents of C16:0, C18:3 and the total IMF in pectoral muscle. The content of C16:0 in genotype CC was significantly higher than CT (P?<?0.01) and TT (P?<?0.01), and the genotype CT was higher than TT (P?<?0.01). The content of C18:3 in genotype TT was significantly higher than CC and CT (P?<?0.01), whereas the genotype CC and CT had no significant difference (P?>?0.05). The content of IMF in genotype CC was significantly higher than CT (P?<?0.01). However, no significant difference was detected between genotype CC and TT or genotype CT and TT (P?>?0.05).     

Evaluation of the Change of Serum Copper and Zinc Concentrations of Dairy Cows with Subclinical Ketosis

Ketosis in dairy cows can lead to poor reproductive success and decreased milk production. Since the serum concentrations of copper (Cu) and zinc (Zn) are closely associated with the health status of cows, we investigated whether serum concentrations of Cu and Zn differed in dairy cows with subclinical ketosis and healthy dairy cows. Blood samples of 19 healthy dairy cows and 15 subclinically ketotic dairy cows were collected from three farms, and the concentrations of β-hydroxybutyrate (BHBA), glucose, non-esterified fatty acids (NEFA), Cu, and Zn were determined. Subclinically ketotic dairy cows had significantly higher BHBA and NEFA levels (p?<?0.01) and lower glucose (p?<?0.01) than healthy dairy cows. Likewise, serum concentrations of Zn were significantly decreased (p?<?0.05) in dairy cows with subclinical ketosis. There was no significant difference observed for serum Cu concentration between healthy and subclinically ketotic dairy cows. This study suggests that a decreased serum Zn concentration could be a cause of decreased reproductive performance in subclinically ketotic dairy cows.     

Impact of drinking of saline water on hemato-biochemical parameters of Black Bengal goats in the selected areas of Bangladesh

Global climatic changes are contaminating ground and surface water sources around the world, resulting in increased salinity. Knowing the animals' typical physiological capability for salinity tolerance without compromising their health is a necessity. The research was undertaken to determine the impacts of drinking water salinity on hemato-biochemical parameters of Black Bengal goats. A total of 40 Black Bengal goats (20 male and 20 female), age ranging from 1 to 5 years, were randomly selected and divided into 2 groups. The animals of group 1 received higher saline water (12 ppt) and those in group 2 received lower saline water (1 ppt) as regular drinking water. Blood parameters of all selected goats were measured. Serum creatinine, uric acid, urea, potassium, sodium, and chloride were significantly higher (P< 0.05) in the animals of group 1 compared with group 2, although serum phosphorous was significantly lower (P < 0.05) in group 1 compared with group 2. There were no significant differences in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose, magnesium, and calcium between the animals of group 1 and 2. AST and magnesium differed significantly (P < 0.05) between young and adult goats in group 1. Glucose and urea levels were slightly higher (P < 0.05) in young goats. In both groups, male goats had significantly higher (P < 0.05) serum potassium and urea levels than female goats. The results suggest that Black Bengal goats of the coastal areas have different salt tolerance capacities based on their age and sex, and adapt to higher salinity by changing kidney functions.     

Performance,Egg Quality Traits,and Serum Metabolite Concentrations of Laying Hens Affected by Dietary Supplemental Chromium Picolinate and Vitamin C Under a Heat-Stress Condition

A 3?×?2 factorial experiment consisting three levels (0, 200, and 400 μg/kg) of chromium (chromium picolinate) and two levels (0 and 250 mg/kg) of vitamin C was employed to evaluate the effects of these dietary supplements on performance, egg quality traits, and serum biochemical parameters of heat-stressed laying hens (Lohmann LSL-Lite) from 66 to 74 weeks of age. Feed intake increased when birds were given either 400 μg/kg chromium or 250 mg/kg vitamin C (P?<?0.05), but the birds that received both chromium and vitamin C consumed feed similar to those that received only chromium. Dietary treatments had no effect on egg production, egg mass, egg volume, feed conversion ratio, and body mass (P?>?0.05). The birds that fed on diet with chromium or vitamin C produced eggs with higher shell mass and thickness compared to the control. Both eggshell mass and thickness decreased when vitamin C and chromium were supplemented simultaneously, and birds given the diet supplemented with 400 μg/kg chromium and 250 mg/kg vitamin C had eggshell mass and thickness similar to those of the control group. The serum concentration of chromium increased due to increasing level of dietary chromium (P?<?0.05). The birds that received diet with chromium and vitamin C had higher serum concentrations of chromium compared to those that received only chromium (P?<?0.05). Similarly, the hens that received chromium and vitamin C had higher serum concentrations of calcium and phosphorus compared to the hens fed with other treatments (P?<?0.05). The birds given with supplemental chromium exhibited lower serum glucose, total cholesterol, and triglycerides concentrations but higher serum albumin and total protein concentrations compared to the other groups (P?<?0.05).     

Ectopic overexpression of swine PPARγ2 upregulated adipocyte genes expression and triacylglycerol in skeletal muscle of mice

Peroxisome proliferator-activated receptor ??2 (PPAR??2) is a key regulator of adipocyte differentiation, fatty acid uptake and storage in mammals. The primary goal of the present study was to investigate the consequences of PPAR??2 overexpression in the muscle. A swine muscle creatine kinase promoter was used to drive swine PPAR??2 (sPPAR??2) overexpression in the muscle of a transgenic mice model. The results showed that the mRNA of multiple adipocyte genes was increased in the skeletal muscle, as evidenced by the up-regulation of fatty acid synthase (2.11-fold, P?<?0.05), lipoprotein lipase (2.08-fold, P?<?0.01), fatty acid-binding protein 4 (14.30-fold, P?<?0.01), and CD36 antigen (5.50-fold, P?<?0.01). Meanwhile, skeletal muscle triacylglycerol was increased (P?<?0.01) and the fatty acid profile of muscle fat was changed in that more polyunsaturated fats acid were augmented. The present study may further serve to develop transgenic pigs with higher intramuscular fat content and improved pork quality.