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The study investigated the effects of increasing content of corn distillers’ dried grains with solubles (DDGS) in the diets of laying ducks on oxidative status, laying performance, egg quality, and egg yolk fatty acid composition. Longyan females (1080) with similar BW at 17 wk of age were randomly assigned to 6 treatment groups, each consisting of 6 replicates of 30 birds. The basal diet (I) was a typical corn-soybean ration while the experimental diets (II to VI) substituted corn DDGS for soybean meal and wheat bran and a small reduction of corn. The level of substitution in diets (II to VI) was 6%, 12%, 18%, 24% and 30%. The experiment lasted for 18 wk. Average egg weight decreased linearly as the level of corn DDGS inclusion increased (P < 0.001). Haugh unit, albumen weight, and proportion declined as linear responses to corn DDGS substitution (P < 0.05), but yolk color linearly increased (P < 0.001); the proportions of oleic (C18:1) and total monounsaturated fatty acids in egg yolk linearly decreased with increasing corn DDGS and many of the key polyunsaturated fatty acids (PUFAs) like linoleic (C18:2n-6), arachidonic (C20:4n-6) and α-linolenic (C18:3n-3) acids linearly increased (P < 0.001), but not those of eicosapentaenoic (C20:5n-3) and docoshexaenoic (C22:6n-3) acids. The PUFAs n-6/n-3 ratio linearly increased with increasing corn DDGS level (P < 0.001). Increasing corn DDGS linearly increased hepatic expression of GPX1, HO-1, and Nrf2 and hepatic activity of GSH-Px and the liver content of MDA (P < 0.001). There were no treatment effects on egg production, egg mass, feed conversion ratio, eggshell thickness, strength, and yolk cholesterol content (P > 0.05). In conclusion, the current study indicates that the use of corn DDGS is possible as a replacement, primarily for soybean meal at levels up to 18% in the diets of laying ducks without affecting laying performance, egg quality, and antioxidant status. Increasing amounts of corn DDGS linearly increased egg yolk concentrations of key fatty acids like like C18:2n-6 and C18:3n-3 and the antioxidant enzyme activity of GSH-Px through the Nrf2 pathway to avoid oxidative stress.