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1.
Neuroscience ; 256: 163-9, 2014 Jan 03.
Article in English | MEDLINE | ID: mdl-24183965

ABSTRACT

During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for 4 weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter 6 weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI.


Subject(s)
Fenbendazole/therapeutic use , Recovery of Function/drug effects , Spinal Cord Injuries , Spinal Cord/pathology , Analysis of Variance , Animals , Disease Models, Animal , Drug Administration Schedule , Female , Immunoglobulin G/metabolism , Leukocyte Common Antigens/metabolism , Mice , Mice, Inbred C57BL , Recovery of Function/physiology , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Time Factors , Trauma Severity Indices
2.
Anim Reprod Sci ; 125(1-4): 180-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21511415

ABSTRACT

Selenium (Se) is an essential component of at least 25 selenoproteins involved in a multitude of physiological functions, including reproduction. However, relatively little is known about the mechanisms by which Se exerts its physiological effects in reproductive tissue. The objective of this study was to compare the effect of long-term inorganic Se (sodium selenite, SS) and organic yeast-derived Se (Sel-Plex(®), SP) supplementations on tissue Se content and gene expression patterns in the oviduct of broiler-breeder hens. Hens were randomly assigned at 6 weeks of age to one of the three treatments: basal semi-purified diet (control), basal diet+0.3 ppm Se as SP or basal diet+0.3 ppm Se as SS. At 49 weeks, oviduct tissue from hens randomly selected from each treatment (n=7) was analyzed for Se content and gene expression profiles using the Affymetrix Chicken genome array. Gene expression data were evaluated using GeneSpring GX 10.0 (Silicon Genetics, Redwood, CA) and Ingenuity Pathways Analysis software (Ingenuity Systems, Redwood City, CA). Oviduct Se concentration was greater with Se supplementation compared with the control (P≤0.05) but did not differ between SS- and SP-supplemented groups. Gene expression analysis revealed that the quantity of gene transcripts associated with energy production and protein translation were greater in the oviduct with SP but not SS supplementation. Targets up-regulated by SP, but not SS, included genes encoding several subunits of the mitochondrial respiratory complexes, ubiquinone production and ribosomal subunits. SS hens showed a decrease in transcripts of genes involved in respiratory complexes, ATP synthesis and protein translation and metabolism in oviduct relative to control hens. In this study, although tissue Se concentrations did not differ between hens fed SS- and SP-supplemented diets, expression patterns of genes involved in energy production and protein synthesis pathways differed between treatments. These variations may partially explain the differences in reproductive performance reported in hens fed different forms of Se.


Subject(s)
Chickens/genetics , Gene Expression Regulation/drug effects , Oviducts/drug effects , Selenium/administration & dosage , Animals , Chickens/metabolism , Computational Biology , Dietary Supplements , Female , Gene Expression Profiling/methods , Gene Expression Profiling/veterinary , Oligonucleotide Array Sequence Analysis/veterinary , Oviducts/metabolism , Oviducts/physiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Random Allocation , Reverse Transcriptase Polymerase Chain Reaction/veterinary
3.
Poult Sci ; 90(1): 136-46, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21177453

ABSTRACT

Previous study indicated that inclusion of an algae-based antioxidant as an antioxidative agent [EconomasE, Alltech, Nicholasville, KY; EcoE] significantly reduced the amount of vitamin E (VE) required in broiler diets without compromising performance and meat quality. To assess the mechanisms related to the VE-saving activity of EcoE, as well as other potential functions related to EcoE and VE supplementation, we analyzed gene expression profiles of breast muscle from broilers fed a control diet, the control diet + 50 IU of VE/kg, the control diet + 100 IU of VE/kg, or the control diet + 200 g of EcoE/ton. Evaluation of the serum antioxidant capacity indicated that dietary supplementation of either a high level of VE (50 or 100 IU of VE/kg) or EcoE significantly improved bird antioxidant status. Analysis of gene expression profiles indicated that expression of 542 genes of the breast muscle were altered (P < 0.05, fold change >1.2) by dietary treatments, of which a significant part were commonly regulated by EcoE and VE (especially the control diet + 50 IU of VE/kg). In addition to the process of cellular oxidation, gene ontology analysis indicated the involvement of EcoE and VE on cell morphology, skeletal and muscular system development and function, immune response, and multiple metabolic processes, including lipid, carbohydrate, and drug metabolism. Results of this experiment indicate that the biological roles of high VE, including its activity as an antioxidant, can be greatly mimicked at the transcriptional level by EcoE, and they suggest a relationship of functional redundancy between VE and EcoE in the broiler diets.


Subject(s)
Antioxidants/pharmacology , Chickens , Diet/veterinary , Gene Expression Regulation/drug effects , Vitamin E/pharmacology , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Antioxidants/chemistry , Gene Expression Profiling/veterinary , Muscle, Skeletal/drug effects , Muscle, Skeletal/metabolism , Yeasts
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