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

ABSTRACT: 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.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6941019 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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

Zhao Yongwei Y Niu Yu Y He Jintian J Zhang Lili L Wang Chao C Wang Tian T

Animals : an open access journal from MDPI 20191213 12

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 incr ...[more]

PMID: 31847280

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Project description:The aim of present study was to evaluate whether diets supplemented with dihydroartemisinin (DHA) could alleviate intestinal inflammatory injury in weaned piglets with intrauterine growth retardation (IUGR). Twelve normal birth weight (NBW) piglets and 12 piglets with IUGR were fed a basal diet (NBW-CON and IUCR-CON groups), and another 12 piglets with IUGR were fed the basal diet supplemented with DHA at 80 mg/kg (IUGR-DHA group) from 21 to 49 d of age. At 49 d of age, 8 piglets with similar body weight in each group were sacrificed. The jejunal and ileal samples were collected for further analysis. The results showed that IUGR impaired intestinal morphology, increased intestinal inflammatory response, raised enterocyte apoptosis and reduced enterocyte proliferation and activated transmembrane toll-like receptor 4 (TLR4)/nucleotide-binding and oligomerization domain (NOD)/nuclear factor-κB (NF-κB) signaling pathway. Dihydroartemisinin inclusion ameliorated intestinal morphology, indicated by increased villus height, villus height-to-crypt depth ratio, villus surface area and decreased villus width of piglets with IUGR (P < 0.05). Compared with NBW piglets, IUGR piglets supplemented with DHA exhibited higher apoptosis index and caspase-3 expression, and lower proliferation index and proliferating cell nuclear antigen expression in the intestine (P < 0.05). Dihydroartemisinin supplementation attenuated the intestinal inflammation of piglets with IUGR, indicated by increased concentrations of intestinal inflammatory cytokines and lipopolysaccharides (P < 0.05). In addition, DHA supplementation down-regulated the related mRNA expressions of TLR4/NOD/NF-κB signaling pathway and upregulated mRNA expressions of negative regulators of TLR4 and NOD signaling pathway in the intestine of piglets with IUGR (P < 0.05). Piglets in the IUGR-DHA group showed lower protein expressions of TLR4, phosphorylated NF-κB (pNF-κB) inhibitor α, nuclear pNF-κB, and higher protein expression of cytoplasmic pNF-κB in the intestine than those in the IUGR-CON group (P < 0.05). In conclusion, DHA supplementation could improve intestinal morphology, regulate enterocyte proliferation and apoptosis, and alleviate intestinal inflammation through TLR4/NOD/NF-κB signaling pathway in weaned piglets with IUGR.

Project description:There are few studies on the mechanism of redox status imbalance and intestinal dysfunction in intrauterine growth restricted (IUGR) newborn piglets. Here, we investigated the mechanism of jejunum dysfunction in weaned piglets with IUGR and the mechanism through which dimethylglycine sodium salt (DMG-Na) supplementation improving the imbalance of their redox status. In this work, a total of 10 normal birth weight (NBW) newborn piglets and 20 IUGR newborn piglets were obtained. After weaning at 21 d, they were assigned to 3 groups (n = 10/group): NBW weaned piglets fed standard basal diets (NBWC); one IUGR weaned piglets fed standard basal diets (IUGRC); another IUGR weaned piglets from the same litter fed standard basal diets plus 0.1% DMG-Na (IUGRD). The piglets in these 3 groups were sacrificed at 49 d of age, and the blood and jejunum samples were collected immediately. The growth performance values in the IUGRC group were lower (P < 0.05) than those in the NBWC group. Jejunum histomorphological parameters, inflammatory cytokines, and digestive enzyme activity as well as serum immunoglobulin were lower (P < 0.05) in the IUGRC group than those in the NBWC group. Compared with these in the NBWC group, the redox status of serum, jejunum, and mitochondria and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were suppressed in the IUGRC group (P < 0.05). However, compared with those in the IUGRC group, the growth performance values, jejunum histomorphological parameters, inflammatory cytokines, digestive enzyme activity, serum immunoglobulin, redox status of serum, jejunum, and mitochondria, and the expression levels of jejunum redox status-related, cell adhesion-related, and mitochondrial function-related genes and proteins were improved (P < 0.05) in the IUGRD group. In conclusion, dietary DMG-Na supplementation alleviates redox status imbalance and intestinal dysfunction in IUGR weaned piglets mainly by activating the sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptorγcoactivator-1α (PGC1α) pathway, thereby improving their unfavorable body state.

Project description:Intrauterine growth retardation (IUGR) results in intestinal dysfunction contributing to metabolic syndrome and growth lag of piglets. Bile acid (BA) presents various bioactivities, including regulation roles in antioxidant, anti-inflammation, and glucose and lipid metabolism. Forty-eight weaned piglets were allocated to four groups in a 2 × 2 factorial arrangement with the effects of BA supplementation and IUGR challenge. Twenty-four IUGR piglets and 24 normal birth weight (NBW) piglets were allocated into two groups, respectively, including the control group fed with a basal diet, and the treatment group fed a basal diet supplemented with 400 mg/kg BA. The experiment lasted 28 days. The results indicated that BA improved liver and spleen indexes in IUGR piglets, whereas decreased blood RDW-CV and RDW-SD regardless of IUGR (P < 0.05). Dietary BA supplementation decreased plasma CAT activity and liver GSH concentration regardless of IUGR, whereas increased plasma GSH and liver H2O2 and decreased liver T-AOC in weaned piglets (P < 0.05). In addition, IUGR downregulated liver Nrf1 and Nrf2 expression levels, while BA supplementation upregulated the Nrf2 expression of liver in weaned piglets (P < 0.05). Dietary BA decreased (P < 0.05) jejunal GSH concentration and ileal CAT activity regardless of IUGR. Furthermore, IUGR upregulated (P < 0.05) jejunal SOD and CAT expression levels; however, dietary BA upregulated ileal Nrf1 (P < 0.05) and Keap1 (P = 0.07) expression levels in piglets regardless of IUGR. Moreover, IUGR upregulated the liver lipid synthesis (FAS) and downregulated HSL and SCD1 expression levels, while dietary BA downregulated liver FAS and SCD1 expression levels (P < 0.05). However, BA supplementation could enhance liver gluconeogenesis by upregulating (P < 0.05) the liver G6PC and PCK1 expression levels in the NBW piglets but not in the IUGR piglets. Collectively, these findings suggest that BA could regulate the redox status of weaned piglets by regulating the Nrf2/Keap1 pathway and improving liver glucose and lipid metabolism of IUGR piglets. These findings will provide a reference for the application of BA in swine production; moreover, considering the physiological similarity between pigs and humans, these findings will provide a reference for IUGR research in humans.

Project description:Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.

Project description:Antioxidant polyphenols from plants are potential dietary supplementation to alleviate early weaning-induced intestinal disorders in piglets. Recent evidences showed polyphenol quercetin could reshape gut microbiota when it functioned as anti-inflammation or antioxidation agents in rodent models. However, the effect of dietary quercetin supplementation on intestinal disorders and gut microbiota of weanling piglets, along with the role of gut microbiota in this effect, both remain unclear. Here, we determined the quercetin's effect on attenuating diarrhea, intestinal damage, and redox imbalance, as well as the role of gut microbiota by transferring the quercetin-treated fecal microbiota to the recipient piglets. The results showed that dietary quercetin supplementation decreased piglets' fecal scores improved intestinal damage by increasing tight junction protein occludin, villus height, and villus height/crypt depth ratio but decreased crypt depth and intestinal epithelial apoptosis (TUNEL staining). Quercetin also increased antioxidant capacity indices, including total antioxidant capacity, catalase, and glutathione/oxidized glutathione disulfide but decreased oxidative metabolite malondialdehyde in the jejunum tissue. Fecal microbiota transplantation (FMT) from quercetin-treated piglets had comparable effects on improving intestinal damage and antioxidative capacity than dietary quercetin supplementation. Further analysis of gut microbiota using 16S rDNA sequencing showed that dietary quercetin supplementation or FMT shifted the structure and increased the diversity of gut microbiota. Especially, anaerobic trait and carbohydrate metabolism functions of gut microbiota were enriched after dietary quercetin supplementation and FMT, which may owe to the increased antioxidative capacity of intestine. Quercetin increased the relative abundances of Fibrobacteres, Akkermansia muciniphila, Clostridium butyricum, Clostridium celatum, and Prevotella copri but decreased the relative abundances of Proteobacteria, Lactobacillus coleohominis, and Ruminococcus bromii. Besides, quercetin-shifted bacteria and carbohydrate metabolites short chain fatty acids were significantly related to the indices of antioxidant capacity and intestinal integrity. Overall, dietary quercetin supplementation attenuated diarrhea and intestinal damage by enhancing the antioxidant capacity and regulating gut microbial structure and metabolism in piglets.

Dataset Information

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

Publications

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

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