γ-tocopherol supplementation inhibits protein nitration and ascorbate oxidation in rats with inflammation

γ-Tocopherol (γT) complements α-tocopherol (αT) by trapping reactive nitrogen oxides to form a stable adduct, 5-nitro-γT [Christen et al., PNAS 94:3217–3222; 1997]. This observation led to the current investigation in which we studied the effects of γT supplementation on plasma and tissue vitamin C, vitamin E, and protein nitration before and after zymosan-induced acute peritonitis. Male Fischer 344 rats were fed for 4 weeks with either a normal chow diet with basal 32 mg αT/kg, or the same diet supplemented with 90mg d-γT/kg. Supplementation resulted in significantly higher levels of γT in plasma, liver, and kidney of control animals without affecting αT, total αT+γT or vitamin C. Intraperitoneal injection of zymosan caused a marked increase in 3-nitrotyrosine and a profound decline in vitamin C in all tissues examined. Supplementation with γT significantly inhibited protein nitration and ascorbate oxidation in the kidney, as indicated by the 29% and 56% reduction of kidney 3-nitrotyrosine and dehydroascorbate, respectively. Supplementation significantly attenuated inflammation-induced loss of vitamin C in the plasma (38%) and kidney (20%). Zymosan-treated animals had significantly higher plasma and tissue γT than nontreated pair-fed controls, and the elevation of γT was strongly accentuated by the supplementation. In contrast, αT did not significantly change in response to zymosan treatment. In untreated control animals, γT supplementation lowered basal levels of 3-nitrotyrosine in the kidney and buffered the starvation-induced changes in vitamin C in all tissues examined. Our study provides the first in vivo evidence that in rats with high basal amounts of αT, a moderate γT supplementation attenuates inflammation-mediated damage, and spares vitamin C during starvation-induced stress without affecting αT.