Source: TUFTS UNIVERSITY submitted to NRP
VITAMIN E AND SELENIUM
Sponsoring Institution
Cooperating Schools of Veterinary Medicine
Project Status
COMPLETE
Funding Source
STATE
Reporting Frequency
Annual
Accession No.
0191521
Grant No.
(N/A)
Cumulative Award Amt.
(N/A)
Proposal No.
(N/A)
Multistate No.
(N/A)
Project Start Date
Oct 1, 1999
Project End Date
Jun 30, 2004
Grant Year
(N/A)
Program Code
[(N/A)]- (N/A)
Recipient Organization
TUFTS UNIVERSITY
200 WESTBORO ROAD
N. GRAFTON,MA 01536
Performing Department
CLINICAL SCIENCES
Non Technical Summary
Free radical-induced injury has been implicated in the development and progression of a number of cardiac diseased, including coronary artery disease, myocardial infarction, and some forms of cardiomyopathy in people and laboratory animals. Using the dog as an animal model, this study is testing the hypothesis that administration of vitamin E, a powerful antioxidant, will combat free-radical injury by increading antioxidant capacity and decrease oxidative stress in dogs afflicted with idiopathic dilated cardiomyopathy.
Animal Health Component
75%
Research Effort Categories
Basic
25%
Applied
75%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
72338301010100%
Knowledge Area
723 - Hazards to Human Health and Safety;

Subject Of Investigation
3830 - Pets (companion animals);

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
Based on data from our previous study showing elevated oxidative stress and decreased vitamin E in dogs with IDCM, we propose to examine the hypothesis : Administration of vitamin E, a powerful antioxidant, will increase antioxidant capacity and decrease oxidative stress in dogs with IDCM, thus improving clinical signs, immune function, and echocardiographic parameters. The specific aims that addresses this hypothesis are as follows: 1.To measure oxidant and antioxidant capacity, physical activity, quality of life, immune function, echocardiographic parameters, and inflammatory mediators in dogs with IDCM. 2.To measure the above parameters after three months of vitamin E or placebo supplementation.
Project Methods
Dogs with Idiopathic Dilated Cardiomyopathy (IDCM) will be studied. A diagnosis of IDCM will be based on the presence of the left atrial enlargement, left ventricular dilation, and fractional shortening <28%(<22% in Doberman pinschers) on 2-D and M-mode echocardiography. Dogs will first be examined on day 7 of the study. A serum biochemistry profile will be measured to assess renal and hepatic function, and to determine if any adjustments to cardiac medications are necessary. Owners will be instructed on completing the 3 day diet record and on measuring activity using the TriTracR3D ergomenter. This ergometer measures activity by integrated acceleration, measures acceleration in all 3 dimensions, and is pre-programmed by the investigator (which decreases the risk of owner-related problems with other activity monitors). Medications will be reviewed and any necessary adjustments will be made. Owners willl be instructed to measure the dog's activity for 24 hours on day 1 and a food record will be kept on 2 weekdays and 1 weekend day between days 7 and 1. Owners will complete a quality of life questionnaire at this time. Dogs will undergo and echocardiogram (standard2D and M mode echocardiographic examination) and fasting blood will be collected for oxidant and antioxidant function, TNF and IL-1 concentrations, and immune function. Dogs will then be randomized to receive one of the following combinations (n=8/group): 1.vitamin E and selenium 2.Vitamin E and placebo 3.Placebo and selenium 4.Placebo and Placebo Investigators and owners will be blinded to the supplements each dog is receiving. Owners will be called at 2 week intervals for progress reports and will be reminded to complete a 3 day diet record between days 77 and 84, and record activity for 24 hours on day 83. Dogs will be reassessed on day 84, at which time all baseline measurements will be repeated. Compliance will be assessed by capsule count. At day 0 and day 84, blood (20mL) will be collected. Plasma vitamin E concentrations will be determined by reverse-phase high performance liquid chromatography, while serum selenium concentration will be determined by flame atomic absorption. Erythrocyte glutathione peroxidase and serum glutathione peroxidase concentrations will be analyzed using a centrifugal analyzer. Oxidative stress will be assessed by plasma malondialdehyde (MDA) concentrations measured by a commercial colorimetric assay. Serum oxygen radical absorbance cpacity (ORAC) will be analyzed on a COBAS FARA II spectrofluorometric analyzer as previously described. The ORAC assay assesses the total antioxidant activity of a sample and is the only method that takes a free radical reaction to completion and uses and 'area under the curve' technique for quantifying antioxidant capacity. Tumor necrosis factor and IL-1 bioactivity will be measured by bioassay (WEHI and D10S cytotoxicity assays, respectively). Immune function will be assessed by mitogen proliferation assays. Activity will be analyzed using the TriTrac interface card software.

Progress 10/01/99 to 06/30/04

Outputs
Concentrations of 8-F2alpha-isoprostane but not MDA or protein carbonyls were significantly higher in the dogs with CHF compared to controls. Vitamin E concentration and GSH:GSSG were significantly lower while ORAC and vitamin C concentration were higher in dogs with CHF compared to controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD.

Impacts
Decreases in some antioxidant defenses and increases in some biomarkers of oxidative stress observed in dogs with CHF appear to be the result of CHF, rather than the underlying disease. The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.

Publications

  • No publications reported this period