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Dietary Dihydroartemisinin Supplementation Attenuates Hepatic Oxidative Damage of Weaned Piglets with Intrauterine Growth Retardation through the Nrf2/ARE Signaling Pathway

College of Animal Science and Technology, Nanjing Agricultural University, No. 6, Tongwei Road, Xuanwu District, Nanjing 210095, China
Author to whom correspondence should be addressed.
Animals 2019, 9(12), 1144;
Received: 18 October 2019 / Revised: 11 December 2019 / Accepted: 11 December 2019 / Published: 13 December 2019
(This article belongs to the Section Pigs)
Intrauterine growth retardation (IUGR) is usually defined as fetal growth below the tenth percentile for gestational age and results in impaired development and growth of the fetus during gestation. In addition to the high rates of perinatal mortality, IUGR has recently been shown to increase the risk of oxidative damage. Therefore, it is important to improve the body’s antioxidant capacity and reduce the oxidative damage caused by IUGR. The nuclear erythroid 2-related factor 2/ antioxidant response element (Nrf2/ARE) signaling pathway plays an important role in the defense against oxidative damage by increasing the activities of antioxidant enzymes. Dihydroartemisinin (DHA) is traditionally used to treat malaria. In addition, DHA has protective effects through increasing the activity of antioxidant enzymes and genes and the protein expression of Nrf2. Our results showed that dietary dihydroartemisinin supplementation improved antioxidant status in piglets with IUGR. Therefore, DHA can alleviate oxidative damage induced by IUGR in animals.
The object of present study was to evaluate the effects of dihydroartemisinin (DHA) supplementation on the hepatic antioxidant capacity in IUGR-affected weaned piglets. Eight piglets with normal birth weight (NBW) and sixteen IUGR-affected piglets were selected. Piglets were weaned at 21 days. NBW and IUGR groups were fed a basal diet and the ID group was fed the basal diet supplemented with 80 mg/kg DHA for 28 days. The result indicated that compared with NBW piglets, IUGR-affected piglets increased (p < 0.05) the concentration of malondialdehyde (MDA) and decreased (p < 0.05) the serum activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In addition, IUGR-affected piglets showed increased (p < 0.05) hepatic concentrations of protein carbonyl (PC), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and oxidized glutathione (GSSG), and an increased GSSG:GSH value. IUGR-affected piglets exhibited lower (p < 0.05) activities of GSH-Px, T-SOD, total antioxidant capacity (T-AOC), and the concentration of glutathione (GSH). DHA supplementation decreased (p < 0.05) the serum concentration of MDA and increased the serum activities of T-AOC, T-SOD, GSH-Px, and CAT. The ID group showed decreased (p < 0.05) concentrations of MDA, PC, 8-OHdG, and GSSG, and a decreased GSSG:GSH value in the liver. The hepatic activity of T-SOD and the concentration of GSH were increased (p < 0.05) in the liver of ID group. IUGR-affected piglets downregulated (p < 0.05) mRNA expression of nuclear erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), and CAT. DHA supplementation increased (p < 0.05) mRNA expression of Nrf2, HO-1, GPx1, and CAT in the ID group. In addition, the protein expression of Nrf2 was downregulated (p < 0.05) in the liver of IUGR-affected piglets and DHA supplementation increased (p < 0.05) the protein content of Nrf2 and HO-1. In conclusion, DHA may be beneficial in alleviating oxidative damage induced by IUGR through the Nrf2/ARE signaling pathway in the liver. View Full-Text
Keywords: dihydroartemisinin; intrauterine growth retardation; liver; oxidative damage dihydroartemisinin; intrauterine growth retardation; liver; oxidative damage
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Zhao, Y.; Niu, Y.; He, J.; Zhang, L.; Wang, C.; Wang, T. Dietary Dihydroartemisinin Supplementation Attenuates Hepatic Oxidative Damage of Weaned Piglets with Intrauterine Growth Retardation through the Nrf2/ARE Signaling Pathway. Animals 2019, 9, 1144.

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