α-Tocopherol Attenuates the Severity of Pseudomonas aeruginosa-induced Pneumonia.

Pseudomonas aeruginosa is a lethal pathogen that causes high mortality and morbidity in immunocompromised and critically ill patients. The type III secretion system (T3SS) of P. aeruginosa mediates many of the adverse effects of infection with this pathogen, including increased lung permeability in a Toll-like receptor 4/RhoA/PAI-1 (plasminogen activator inhibitor-1)-dependent manner. α-Tocopherol has antiinflammatory properties that may make it a useful adjunct in treatment of this moribund infection. We measured transendothelial and transepithelial resistance, RhoA and PAI-1 activation, stress fiber formation, P. aeruginosa T3SS exoenzyme (ExoY) intoxication into host cells, and survival in a murine model of pneumonia in the presence of P. aeruginosa and pretreatment with α-tocopherol. We found that α-tocopherol alleviated P. aeruginosa-mediated alveolar endothelial and epithelial paracellular permeability by inhibiting RhoA, in part, via PAI-1 activation, and increased survival in a mouse model of P. aeruginosa pneumonia. Furthermore, we found that α-tocopherol decreased the activation of RhoA and PAI-1 by blocking the injection of T3SS exoenzymes into alveolar epithelial cells. P. aeruginosa is becoming increasingly antibiotic resistant. We provide evidence that α-tocopherol could be a useful therapeutic agent for individuals who are susceptible to infection with P. aeruginosa, such as those who are immunocompromised or critically ill.

Distribution of injected fat-soluble vitamins in plasma and tissues of nursery pigs.

OBJECTIVE: The objective of this experiment was to investigate the effects of fat-soluble vitamin injection on plasma and tissue vitamin status in nursery pigs. METHODS: A total of 16 pigs (initial body weight: 7.15±1.1 kg) were allotted to 2 treatments at d 7 post-weaning. Pigs were fed a corn-soybean meal-based basal diet with no supplemental vitamin A and i.m. injected with 300,000 IU of retinyl palmitate, 900 IU of d-α-tocopherol and 30,000 IU of vitamin D3 with control pigs having no vitamin injection. Blood (d 0, 3, 7, and 14 post-injection) and tissue samples (liver, brain, heart, lung, and muscle; d 7 and 14 post-injection) were collected from pigs. Retinyl palmitate, retinol, and α-tocopherol concentrations were analyzed in plasma and tissues, while plasma was assayed for 25-hydroxycholecalciferol (25-OHD3). RESULTS: Plasma retinol and 25-OHD3 concentrations increased by the vitamin injection from d 3 to 14 post-injection (p<0.05) whereas plasma retinyl palmitate was detected only in the vitamin treatment at d 3 and 7 post-injection (115.51 and 4.97 µg/mL, respectively). Liver retinol, retinyl palmitate, and retinol+retinyl palmitate concentrations increased by retinyl palmitate injection at d 7 and 14 post-injection (p<0.05) whereas those were not detected in the other tissues. The d-α-tocopherol injection increased α-tocopherol concentrations in plasma at d 3 and 7 post-injection (p<0.05) and in liver, heart (p<0.10), and muscle (p<0.05) at d 7 post-injection. CONCLUSION: Fat-soluble vitamin injection increased plasma status of α-tocopherol, retinol, retinyl palmitate and 25-OHD3. As plasma levels decreased post-injection, vitamin A level in liver and vitamin E level in muscle, heart and liver increased. The α-tocopherol found in plasma after injection was distributed to various tissues but retinyl palmitate only to the liver.

Administration of vitamin D3 by injection or drinking water alters serum 25-hydroxycholecalciferol concentrations of nursery pigs.

OBJECTIVE: Two experiments were conducted to evaluate vitamin D3 administration to nursery pigs by injection or in drinking water on serum 25-hydroxycholecalciferol (25-OHD3) concentrations. METHODS: At weaning, 51 pigs (27 and 24 pigs in experiments 1 and 2, respectively) were allotted to vitamin D3 treatments. Treatments in experiment 1 were: i) control (CON), no vitamin administration beyond that in the diet, ii) intramuscular (IM) injection of 40,000 IU of vitamin D3 at weaning, and iii) water administration, 5,493 IU of vitamin D3/L drinking water for 14 d postweaning. Treatments in experiment 2 were: i) control (CON), no vitamin administration, and ii) water administration, 92 IU of d-α-tocopherol and 5,493 IU of vitamin D3/L drinking water for 28 d postweaning. The lightest 2 pigs within each pen were IM injected with an additional 1,000 IU of d-α-tocopherol, 100,000 IU of retinyl palmitate, and 100,000 IU of vitamin D3. RESULTS: In both experiments, serum 25-OHD3 was changed after vitamin D3 administration (p<0.05). In experiment 1, injection and water groups had greater values than CON group through d 35 and 21 post-administration, respectively (p<0.05). In experiment 2, serum values peaked at d 3 post-administration in the injection groups regardless of water treatments (p<0.05) whereas CON and water-only groups had peaks at d 14 and 28 post-administration, respectively (p<0.05). Even though the injection groups had greater serum 25-OHD3 concentrations than the non-injection groups through d 7 post-administration regardless of water treatments (p<0.05), the water-only group had greater values than the injection-only group from d 21 post-administration onward (p<0.05). CONCLUSION: Serum 25-OHD3 concentrations in pigs increased either by vitamin D3 injection or drinking water administration. Although a single vitamin D3 injection enhanced serum 25-OHD3 concentrations greater than water administration in the initial period post-administration, a continuous supply of vitamin D3 via drinking water could maintain higher serum values than the single injection.

Influence of specific management practices on blood selenium, vitamin E, and beta-carotene concentrations in horses and risk of nutritional deficiency.

BACKGROUND: Selenium or alpha-tocopherol deficiency can cause neuromuscular disease. Beta-carotene has limited documentation in horses. OBJECTIVE: To evaluate the effect of owner practices on plasma beta-carotene concentration and risk of selenium and alpha-tocopherol deficiencies. ANIMALS: Three-hundred and forty-nine adult (≥1 year), university and privately owned horses and mules. METHODS: Cross-sectional study. Whole blood selenium, plasma alpha-tocopherol, and plasma beta-carotene concentrations were measured once. Estimates of daily selenium and vitamin E intake, pasture access, and exercise load were determined by owner questionnaire. Data were analyzed using t tests, Mann-Whitney tests, parametric or nonparametric analysis of variance (ANOVA), Kruskal-Wallis test, Spearman's correlation and contingency tables (P < .05). RESULTS: Nearly 88% of the horses received supplemental selenium; 71.3% received ≥1 mg/d. Low blood selenium concentration (<80 ng/mL) was identified in 3.3% of horses, and 13.6% had marginal concentrations (80-159 ng/mL). Non-supplemented horses were much more likely to have low blood selenium (odds ratio [OR], 20.2; 95% confidence interval [CI], 9.26-42.7; P < .001). Supplemental vitamin E was provided to 87.3% of horses; 57.7% received ≥500 IU/d. Deficient (<1.5 µg/mL) and marginal (1.5-2.0 µg/mL) plasma (alpha-tocopherol) occurred in 15.4% and 19.9% of horses, respectively. Pasture access (>6 h/d) and daily provision of ≥500 IU of vitamin E was associated (P < .001) with higher plasma alpha-tocopherol concentrations. Plasma beta-carotene concentration was higher in horses with pasture access (0.26 ± 0.43 versus 0.12 ± 0.13 µg/mL, P = .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Suboptimal blood selenium and plasma alpha-tocopherol concentrations occurred in 16.7% and 35.5% of horses, respectively, despite most owners providing supplementation. Inadequate pasture access was associated with alpha-tocopherol deficiency, and reliance on selenium-containing salt blocks was associated with selenium deficiency.