Short-term alpha- or gamma-delta-enriched tocopherol oil supplementation differentially affects the expression of proinflammatory mediators: selective impacts on characteristics of protein tyrosine nitration in vivo

While vitamin E has been used for decades in cattle diets, the principle form used traditionally is the synthetic α-isoform acetate or succinate and largely no data exist on the biological partitioning or functionality of the major naturally occurring γ- and δ-isoforms in cattle. Using tyrosine 3’-nitrated protein (pNT) as a biomarker of nitrosative cell stress, we sought to evaluate the effectiveness of short-term feeding supplementation of high content natural α-tocopherol (α-T, 96% α-isomer) compared to high content γ- and δ-enriched low α-content mixed tocopherol oils (γ-T, ~70% γ-, 20% δ-, <5% α-isoform) to mitigate systemic and hepatic aspects of the proinflammatory response to endotoxin (LPS). Calves fed diets supplemented with α-T, γ-T for five days or no tocopherol supplement (T0E) were challenged with a low-level of LPS (0.25 μg/kg, iv, E. coli 055:B5) sufficient to effect a liver nitration response. As fed, α-T or γ-T increased plasma and liver content of the respective tocopherols reflecting their relative abundance in the respective diets. Plasma or tissue mediators and biomarkers of the proinflammatory response [plasma concentrations of tumor necrosis factor-α (TNF-α, P<0.001), nitrate+nitrite (NOx, P<0.01), and serum amyloid A (SAA, P<0.001)], and general liver content of pNT (P<0.005) increased after LPS. LPS-mediated increases in TNF-α were not dif- ferent between diet treatments; both plasma NOx (P<0.05) and generalized liver pNT (P<0.03) responses were attenuated significantly in α-T and γ-T versus T0E calves. Plasma SAA was significantly decreased in γ-T calves at 24 h post-LPS relative to responses in α-T or T0E calves. The nitration of the mitochondrial proteins 24 h post-LPS was not only attenuated in α-T and γ-T vs T0E, but also the mitigating effect of γ-T on these specific nitration events was greater than that of α-T (P<0.01). Results are consistent with the concept that short-term α-T or γ-T supplementation can effectively decrease proinflammatory liver pNT after LPS; some mitochondrial nitration targets may be better protected with prophylactic supplementation with γ-,δ-tocopherol enriched oil.