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1.
Nutrition ; 81: 110940, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32755743

RESUMO

OBJECTIVES: The aim of the present study was to investigate the potential of pterostilbene, a beneficial component primarily found in blueberries, to alleviate the intrauterine growth retardation (IUGR)-induced early liver injury and oxidative stress in a porcine model. METHODS: Thirty-six IUGR piglets and an equal number of normal birth weight (NBW) counterparts received a diet with or without pterostilbene (250 mg/kg diet) during the first week post-weaning. Parameters related to the hepatic injury, oxidative stress, and antioxidant defense mechanisms were analyzed. RESULTS: Relative to NBW, IUGR induced liver injury, which corresponded to increments in circulating alanine transaminase activity and hepatic apoptotic cell rate, superoxide radical generation, and the accumulation of oxidative damage products (P < 0.05). Administering pterostilbene reduced plasma transaminase activities, decreased hepatocyte apoptosis rate, and prevented the augmented levels of hepatic superoxide anion, 8-hydroxy-2 deoxyguanosine, and 4-hydroxynonenal-modified protein (P < 0.05). In terms of the hepatic antioxidant function, pterostilbene was efficient in improving the superoxide dismutase activity and the metabolic cycle between reduced glutathione and its oxidized form (P < 0.05). The pterostilbene-supplemented diet facilitated the nuclear translocation of nuclear factor erythroid-2-related factor 2 (NRF2) and promoted the expression levels of superoxide dismutase 2 in the liver of IUGR piglets (P < 0.05). CONCLUSION: This study indicates that pterostilbene treatment has an auxiliary therapeutic potential to ameliorate early liver injury in IUGR neonates, presumably by stimulating the NRF2 signals and the associated antioxidant function.

2.
Food Funct ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300526

RESUMO

Mitochondrial dysfunction, oxidative stress and inflammation are crucial contributors to liver damage and nonalcoholic fatty liver disease (NAFLD) in adulthood in offspring affected by intrauterine growth retardation (IUGR). Resveratrol (RSV) has been reported to treat and/or prevent hepatic diseases under various pathological conditions. However, the therapeutic and/or preventive effects of RSV on hepatic abnormality in IUGR adults have not been investigated until now. The effects of IUGR and RSV on the hepatic metabolic status, mitochondrial function, redox homeostasis and inflammation in pigs in adulthood were investigated. A total of 36 pairs of IUGR and normal birth weight piglets were orally fed with 80 mg RSV per kg body weight per d or vehicle (0.5% carboxymethylcellulose) for 7-21 d after birth. And then the offspring were fed with a basal diet supplemented with 300 mg RSV per kg feed or a basal diet from weaning to slaughter at 150 d. The plasma and liver samples were collected for subsequent analysis. RSV exerted beneficial effects on hepatic injury and metabolic alterations in IUGR pigs, which may be due to improved mitochondrial function and fatty acid oxidation by intensified mitochondrial biogenesis, enhanced antioxidant levels such as glutathione reductase and total superoxide dismutase activities, increased interleukin 10 gene expression and repolarization of macrophages. RSV alleviated hepatic lipid accumulation in IUGR pigs by improving mitochondrial function, redox status and inflammation, implying that it is a potential candidate for further development as an effective clinical treatment for NAFLD associated with IUGR.

3.
J Anim Sci ; 98(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33027517

RESUMO

This investigation evaluated the potential of natural antioxidants, pterostilbene (PT) and its parent compound resveratrol (RSV), to alleviate hepatic damage, redox imbalance, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in early-weaned piglets. A total of 144 suckling piglets were randomly assigned to four treatments (six replicates per group, n = 6): 1) sow reared, 2) early weaned and fed a basal diet, 3) early weaned and fed the basal diet supplemented with 300 mg/kg PT, or with 4) 300 mg/kg RSV. Early weaning increased plasma alanine aminotransferase (P = 0.004) and aspartate aminotransferase (P = 0.009) activities and hepatic apoptotic rate (P = 0.001) in piglets compared with the sow-reared piglets. Early weaning decreased hepatic adenosine triphosphate (ATP; P = 0.006) content and mitochondrial complexes III (P = 0.019) and IV activities (P = 0.038), but it increased superoxide anion accumulation (P = 0.026) and the expression levels of ER stress markers, such as glucose-regulated protein 78 (P < 0.001), CCAAT/enhancer-binding protein-homologous protein (P = 0.001), and activating transcription factor (ATF) 4 (P = 0.006). PT was superior to RSV at mitigating liver injury and oxidative stress after early weaning, as indicated by decreases in the number of apoptotic cells (P = 0.036) and the levels of superoxide anion (P = 0.002) and 8-hydroxy-2 deoxyguanosine (P < 0.001). PT increased mitochondrial deoxyribonucleic acid content (P = 0.031) and the activities of citrate synthase (P = 0.005), complexes I (P = 0.004) and III (P = 0.011), and ATP synthase (P = 0.041), which may contribute to the mitigation of hepatic ATP deficit (P = 0.017) in the PT-treated weaned piglets. PT also prevented increases in the ER stress marker and ATF 6 expression levels and in the phosphorylation of inositol-requiring enzyme 1 alpha caused by early weaning (P < 0.05). PT increased sirtuin 1 activity (P = 0.031) in the liver of early-weaned piglets than those in the early-weaned piglets fed a basal diet. In conclusion, PT supplementation alleviates liver injury in weanling piglets probably by inhibiting mitochondrial dysfunction and ER stress.

4.
Biomed Res Int ; 2020: 7402645, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733952

RESUMO

Abnormal lipid metabolism, oxidative stress (OS), and inflammation play a pivotal role in the increased susceptibility to neonatal fatty liver diseases associated with intrauterine growth retardation (IUGR). This study was firstly conducted to investigate whether resveratrol could alleviate IUGR-induced hepatic lipid accumulation, alteration of redox and immune status in a sucking piglet model and explore the possible mechanisms at transcriptional levels. A total of 36 pairs of 7 d old male normal birth weight (NBW) and IUGR piglets were orally fed with either 80 mg resveratrol/kg body weight/d or 0.5% carboxymethylcellulose sodium for a period of 14 days, respectively. Compared with the NBW piglets, the IUGR piglets displayed compromised growth performance and liver weight, reduced plasma free fatty acid (FFA) level, increased hepatic OS, abnormal hepatic lipid accumulation and weakened hepatic immune function, and hepatic aberrant transcriptional expression of some genes such as heme oxygenase 1, superoxide dismutase 1, sterol regulatory element-binding protein 1c, stearoyl-CoA desaturase 1, liver fatty acid-binding proteins 1, toll-like receptor 4, and tumor necrosis factor alpha (TNF-α). Oral administration of resveratrol to piglets decreased the levels of FFA and total triglycerides (TG) in the plasma and hepatic TNF-α concentration, and increased glutathione reductase activity and reduced glutathione level in the liver. Resveratrol restored the increased alanine aminotransferase activity in the plasma of IUGR piglets. Treatment with resveratrol ameliorated the increased hepatic malondialdehyde, protein carbonyl, TG, and FFA concentrations induced by IUGR. Resveratrol treatment alleviated the reduced lipoprotein lipase activity and its mRNA expression as well as TNF-α gene expression in the liver of IUGR piglets. Hepatic glutathione peroxidase 1 and monocyte chemotactic protein 1 genes expression of piglets was upregulated by oral resveratrol administration. In conclusion, resveratrol administration plays a beneficial role in hepatic redox status and lipid balance of the IUGR piglets.

5.
Animals (Basel) ; 10(7)2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32708214

RESUMO

The liver is an organ that produces large amounts of reactive oxygen species (ROS). Human infants or piglets are prone to oxidative damage due to their uncompleted development of the antioxidant system, causing liver disease. Piceatannol (PIC) has been found to have significant antioxidant effects. The aim of this experiment was to investigate the effects of PIC on the liver in piglets experiencing oxidative stress caused by diquat (DQ). After weaning, 54 male piglets (Duroc × [Landrace × Yorkshire]) were selected and randomly divided into three treatment groups: the CON group, the DQ-CON group, and the DQ-PIC group. The two challenged groups were injected with DQ and then orally administrated either PIC or another vehicle solution, while the control group was given sterile saline injections and an orally administrated vehicle solution. Compared to the results of the CON group, DQ increased the percentage of apoptosis cells in the liver, also decreased the amount of reduced glutathione (GSH) and increased the concentration of malondialdehyde (MDA). In addition, the adenosine triphosphate (ATP) production, activities of mitochondrial complex I, II, III, and V, and the protein expression level of sirtuin 1 (SIRT1) were inhibited by DQ. Furthermore, PIC supplementation inhibited the apoptosis of hepatic cells caused by DQ. PIC also decreased MDA levels and increased the amount of GSH. Piglets given PIC supplementation exhibited increased activities of mitochondrial complex I, II, III, and V, the protein expression level of SIRT1, and the ATP production in the liver. In conclusion, PIC affected the liver of piglets by improving redox status, preserving mitochondrial function, and preventing excessive apoptosis.

6.
J Anim Sci Biotechnol ; 11: 52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32514341

RESUMO

Background: Evidence indicates that early weaning predisposes piglets to intestinal oxidative stress and increases the risk of intestinal dysfunction; however, there are minimal satisfactory treatment strategies for these conditions. This study investigated the potential of resveratrol and its analog, pterostilbene, as antioxidant protectants for regulating intestinal morphology, barrier function, and redox status among weanling piglets. Methods: A total of 144 piglets were selected at 21 days of age and randomly allocated into one of four treatment groups, each of which included six replicates. Piglets in a sow-reared control group were suckling normally between ages 21 and 28 days, while those in weaned groups were fed a basal diet, supplemented with either 300 mg/kg of resveratrol or with 300 mg/kg of pterostilbene. Parameters associated with intestinal injury and redox status were analyzed at the end of the feeding trial. Results: Early weaning disrupted the intestinal function of young piglets, with evidence of increased diamine oxidase activity and D-lactate content in the plasma, shorter villi, an imbalance between cell proliferation and apoptosis, an impaired antioxidant defense system, and severe oxidative damage in the jejunum relative to suckling piglets. Feeding piglets with a resveratrol-supplemented diet partially increased villus height (P = 0.056) and tended to diminish apoptotic cell numbers (P = 0.084) in the jejunum compared with those fed a basal diet. Similarly, these beneficial effects were observed in the pterostilbene-fed piglets. Pterostilbene improved the feed efficiency of weanling piglets between the ages of 21 and 28 days; it also resulted in diminished plasma diamine oxidase activity and D-lactate content relative to untreated weaned piglets (P < 0.05). Notably, pterostilbene restored jejunal antioxidant capacity, an effect that was nearly absent in the resveratrol-fed piglets. Pterostilbene reduced the malondialdehyde and 8-hydroxy-2´-deoxyguanosine contents of jejunal mucosa possibly through its regulatory role in facilitating the nuclear translocation of nuclear factor erythroid-2-related factor 2 and the expression levels of NAD(P)H quinone dehydrogenase 1 and superoxide dismutase 2 (P < 0.05). Conclusions: The results indicate that pterostilbene may be more effective than its parent compound in alleviating early weaning-induced intestinal damage and redox imbalance among young piglets.

7.
Mol Nutr Food Res ; 64(14): e2000105, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32529694

RESUMO

SCOPE: Endoplasmic reticulum (ER) stress is widely recognized as a critical factor linked to lipid metabolic disorders in nonalcoholic fatty liver disease. However, its pathogenesis remains elusive, and therapeutic options are limited. This study investigates the potential of resveratrol (RSV) to alleviate hepatic steatosis and injury in a tunicamycin (TM)-induced murine ER stress model and provides detailed evidence. METHODS AND RESULTS: Male C57BL/6J mice were orally administered either RSV or vehicle for 2 weeks before the TM challenge. Results indicated that TM induced ER morphological damage and severe unfolded protein reaction (UPR), accompanied by increases in lipid accumulation, oxidative damage, and inflammatory response. Administering RSV decreased the expression of ER stress markers, partially normalized the active levels of UPR sensors, and facilitated sirtuin 1 activity in the liver under ER stress. Notably, the TM-induced hepatic steatosis was also alleviated by RSV, possibly by regulating the expression pattern of genes involving lipid oxidation and delivery. Consistently, RSV attenuated the TM-induced increases in lipid peroxidation, hepatocyte apoptosis, and the overactivation of inflammatory signals. CONCLUSION: RSV may have an auxiliary therapeutic potential to prevent the development of steatosis and its progression to steatohepatitis in the liver by alleviating severe ER stress.

8.
Food Funct ; 11(5): 4202-4215, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32352466

RESUMO

This study investigated the potential of resveratrol (RSV) and its derivative pterostilbene (PT) to prevent diquat (DQ)-induced hepatic oxidative damage and mitochondrial dysfunction in piglets. Seventy-two weanling piglets were randomly divided into the following treatment groups: non-challenged control group, DQ-challenged control group, and DQ-challenged groups supplemented with either 300 mg RSV per kg of diet or an equivalent amount of PT. Each treatment group consisted of six replicates with three piglets per replicate (n = 6). After a two-week feeding trial, piglets were intraperitoneally injected with either 10 mg DQ per kg of body weight or sterile saline. At 24 hours post-injection, one piglet from each replicate (six piglets per treatment) was randomly selected for sample collection and biochemical analysis. Compared with the DQ-challenged control group, PT attenuated the growth loss of piglets after the DQ challenge (P < 0.05). Administration of PT was more effective than its parent compound in inhibiting the DQ-induced hepatic apoptosis and the increased generation of total cholesterol, superoxide anion, and lipid peroxidation products (P < 0.05). Specifically, PT facilitated nuclear factor erythroid 2-related factor 2 signals and the expression and activity of manganese superoxide dismutase, while it also prevented mitochondrial swelling, membrane potential collapse, and adenosine triphosphate depletion, possibly through the activation of sirtuin 1 (P < 0.05). These results indicate that PT may be superior to RSV as an antioxidant to protect the liver of young piglets from oxidative insults.

9.
J Anim Sci ; 98(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31822918

RESUMO

The present study explored the potential effect of pterostilbene as a prophylactic treatment on the lipopolysaccharide (LPS)-induced intestinal injury of broiler chickens by monitoring changes in mucosal injury indicators, redox status, and inflammatory responses. In total, 192 one-day-old male Ross 308 broiler chicks were randomly divided into four groups. This trial consisted of a 2 × 2 factorial design with a diet factor (supplemented with 0 or 400 mg/kg pterostilbene from 1 to 22 d of age) and a stress factor (intraperitoneally injected with saline or LPS at 5.0 mg/kg BW at 21 da of age). The results showed that LPS challenge induced a decrease in BW gain (P < 0.001) of broilers during a 24-h period postinjection; however, this decrease was prevented by pterostilbene supplementation (P = 0.031). Administration of LPS impaired the intestinal integrity of broilers, as indicated by increased plasma diamine oxidase (DAO) activity (P = 0.014) and d-lactate content (P < 0.001), reduced jejunal villus height (VH; P < 0.001) and the ratio of VH to crypt depth (VH:CD; P < 0.001), as well as a decreased mRNA level of jejunal tight junction protein 1 (ZO-1; P = 0.002). In contrast, pterostilbene treatment increased VH:CD (P = 0.018) and upregulated the mRNA levels of ZO-1 (P = 0.031) and occludin (P = 0.024) in the jejunum. Consistently, pterostilbene counteracted the LPS-induced increased DAO activity (P = 0.011) in the plasma. In addition, the LPS-challenged broilers exhibited increases in nuclear accumulation of nuclear factor kappa B (NF-κB) p65 (P < 0.001), the protein content of tumor necrosis factor α (P = 0.033), and the mRNA abundance of IL-1ß (P = 0.042) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3; P = 0.019). In contrast, pterostilbene inhibited the nuclear translocation of NF-κB p65 (P = 0.039) and suppressed the mRNA expression of IL-1ß (P = 0.003) and NLRP3 (P = 0.049) in the jejunum. Moreover, pterostilbene administration induced a greater amount of reduced glutathione (P = 0.017) but a lower content of malondialdehyde (P = 0.023) in the jejunum of broilers compared with those received a basal diet. Overall, the current study indicates that dietary supplementation with pterostilbene may play a beneficial role in alleviating the intestinal damage of broiler chicks under the conditions of immunological stress.


Assuntos
Galinhas/fisiologia , Suplementos Nutricionais/análise , Estilbenos/administração & dosagem , Estresse Fisiológico/imunologia , Animais , Biomarcadores/metabolismo , Galinhas/genética , Galinhas/imunologia , Dieta/veterinária , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Lipopolissacarídeos/efeitos adversos , Masculino , Malondialdeído/metabolismo , Ocludina/metabolismo , RNA Mensageiro/genética , Distribuição Aleatória
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