Animals
·
2025
·Vol. 15
·期 4
·559
·
IF 2.7
Chunjie Hou,Zirou Yu,Chenyu Shi,Ya Huang,Hu Liu
Oxidative stress caused by weaning is widespread in pig breeding and poses a serious threat to the health of piglets. As a feed additive, Brown algae polysaccharides (BAPs) have a good application prospect and have antibacterial, anti-inflammatory, antioxidant, and antiviral activities. The present study was conducted to investigate the effects of BAP on oxidative stress in piglets. The results showed that BAPs alleviated the oxidative stress damage caused by diquat and improved the antioxidant capacity and intestinal barrier capacity of weaned piglets and IPEC-J2 cells. It is worth noting that BAPs also promoted the translocation of Nrf2 from the cytoplasm to the nucleus. These results provide a new way to illustrate the mechanism of BAPs alleviating oxidative stress in piglets. This study investigated the effect of Brown algae polysaccharides (BAPs) on diquat-induced oxidative stress in piglets and IPEC-J2 cells through Nrf2/ARE signaling pathway. In the in vivo model, 24 male piglets of the Duroc × Landrace × Large White breed were selected and divided into 4 groups (n = 6), including the CON group (basal diet), DIQ group (10 mg/kg Diquat), BAP group (1000 mg/kg BAP), and BAP+DIQ group (1000 mg/kg BAP + 10 mg/kg Diquat). Compared with the DIQ group, BAP improved growth performance and the BAP+DIQ group reduced the levels of IL-1β, IL-6, TNF-α, and DAO in plasma, increased VH and VCR, improved jejunal tissue morphology, decreased MDA levels, and increased T-AOC ( p < 0.05). Additionally, the BAP+DIQ group elevated mRNA levels of ZO-1 , and enhanced the protein levels of Occludin, Claudin1, CAT, SOD1, and HO-1 ( p < 0.05). In the in vitro model, the BAP+DIQ group decreased MDA levels, increased T-AOC, elevated mRNA levels of ZO-1 , CAT and SOD2 , as well as protein levels of Claudin1, SOD1, HO-1, and total Nrf2 compared with the DIQ group ( p < 0.05). Furthermore, BAP increased nuclear Nrf2 protein levels, and promoted the translocation of Nrf2 from the cytoplasm to the nucleus compared with the DIQ group ( p < 0.05). In conclusion, BAPs are crucial for enhancing piglets’ antioxidant capacity via Nrf2 pathway activation. These findings highlight BAP’s potential as a natural feed additive to mitigate oxidative stress and improve overall health in piglets. Further research is warranted to explore BAPs as a dietary supplement to support gut health and reduce oxidative stress.
研究领域:
动物营养学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MOLECULAR MEDICINE
·
2020
·Vol. 20
·期 4
·307-317
·
IF 1.6
Yang Yuan,Huang Jin,Li Jianzhong,Yang Huansheng,Yin Yulong
Background: Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated.
Methods: In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited
the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Results: Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations
inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible
for normal acidic lysosomes. Conclusion: In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high
concentrations.
研究领域:
细胞生物学
·
分子生物学
·
动物生理学
✓ 已验证
DOI
PubMed
高影响因子
Food Science and Human Wellness
·
2024
·
IF 5.6
Fangfang Yan,Qun Lu,Chengming Wang,Rui Liu
Our previous study has revealed that procyanidin A 1 (A 1 ) and its simulated digestive product (D-A 1 ) can alleviate acrylamide (ACR)-induced intestine cell damage. However, the underlying mechanism remains unknown. In this study, we elucidated the molecular mechanism for A 1 and D-A 1 to alleviate ACR-stimulated IPEC-J2 cell damage. ACR slightly activated nuclear factor erythroid 2-related factor 2 (Nrf2) signaling and its target genes, but this activation could not reduce intestine cell damage. A 1 and D-A 1 could alleviate ACR-induced cell damage, but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA (siRNA). Further investigation confirmed that A 1 and D-A 1 interacted with Kelch-like ECH-associated protein 1 (Keap1), which boosted the stabilization of Nrf2, subsequently promoted the translocation of Nrf2 into the nucleus, and further increased the expression of antioxidant proteins, thereby inhibiting glutathione (GSH) consumption, maintaining redox balance and eventually alleviating ACR-induced cell damage. Importantly, there was no difference between A 1 and D-A 1 treated groups, indicating that A 1 can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Antioxidants
·
2025
·Vol. 14
·期 8
·914
·
IF 6.6
Pengxin Jiang,Kangping Liu,Yanan Cui,Puyu Liu,Xutao Wang,Zijuan Hou,Jiamei Cui,Ning Chen,Jinghui Fan,Jianguo Li,Yuzhu Zuo,Yan Li
EnterotoxigenicEscherichia coli(ETEC) leads to severe diarrhea in piglets. Naringenin (Nar), a natural flavonoid compound, is known for its antibacterial and anti-antioxidant properties. However, the protective effects of Nar against ETEC-induced diarrhea have not been reported yet. This study investigated the protective mechanisms of Nar against ETEC infection in porcine intestinal epithelial cells (IPEC-J2). ETEC infection induced oxidative stress and ferroptosis in IPEC-J2 cells by elevating intracellular iron content and ROS accumulation, increasing MDA levels, downregulating SOD activity and GPX4 expression, and upregulating the transcription of CHAC1 and SLC7A11. In contrast, Nar suppressed ETEC-induced ferroptosis of IPEC-J2 cells by inhibiting the SLC7A11/GPX4 pathway. Specifically, Nar mitigated mitochondrial damage, reduced intracellular iron levels and ROS accumulation, and ultimately reversed the oxidative stress. Network pharmacology and molecular docking identified heat-shock protein 90 (HSP90) as a potential target of Nar. Overexpression and knockdown experiments revealed that ETEC-induced ferroptosis was mediated by upregulation of HSP90, while the protective effects of Nar against ETEC-induced ferroptosis were dependent on the downregulation of HSP90. In conclusion, Nar targets host HSP90 to protect IPEC-J2 cells from ferroptosis caused by ETEC infection. This study demonstrates that Nar is a potent antioxidant natural compound with potential for preventing ETEC-induced intestinal damage.
研究领域:
兽医学
·
微生物学
·
药理学
·
细胞生物学
·
分子生物学
·
天然产物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2022
·
IF 10.723
Kai Na,Jiani Wei,Li Zhang,Ying Fang,Xiangyu Li,Shuang Lu,Xiaohua Guo
Chitosan oligosaccharides (COS) show the potential to support the intestinal health, but the mechanism and role of COS-derived intestinal microbiota are unknown. We explored the protective effect of direct administration of COS on intestinal barrier function using an in vivo colitis mouse model and an in vitro enterotoxigenic Escherichia coli (ETEC)-challenged IPEC-J2 cell model. COS directly enhanced the intestinal barrier function. COS intervention also promoted the abundance and diversity of intestinal flora. Importantly, FMT intervention with a COS-derived microbiome decreased the disease index level and alleviated histopathological changes, and improved gut barrier function in the colitis model. Both COS and COS-derived microbiota suppressed ETEC-induced cellular apoptosis in IPEC-J2 cells. This study firstly confirms transplantation of COS-modified fecal microbiota can enhance the intestinal barrier function. The mechanism underlying COS benefits is due to a direct intervention by COS supplementation and an indirect improvement of the gut microbiota induced by COS exposure.
研究领域:
胃肠病学
·
微生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2024
·
IF 8.7
Gong Li,Lu Han,Li-Juan Xia,Ang Gao,Zhi-Peng Li,Shi-Ying Zhou,Lei Wan,Yao Deng,Tian-Hong Zhou,Xin-Yi Lu,Yang Luo,Dun-Sheng Liang,Gui-Ting Wu,Sheng-Qiu Tang,Xin-Lei Lian,Hao Ren,Xiao-Ping Liao,Liang Chen,Jian Sun
Plasmid-mediated conjugative transfer of antibiotic resistance genes (ARGs) within the human and animal intestine represents a substantial global health concern. linoleic acid (LA) has shown promise in inhibiting conjugation in vitro , but its in vivo effectiveness in the mammalian intestinal tract is constrained by challenges in efficiently reaching the target site. Recent advancements have led to the development of waterborne polyurethane nanoparticles for improved drug delivery. In this study, we synthesized four waterborne polyurethane nanoparticles incorporating LA (WPU@LA) using primary raw materials, including N-methyldiethanolamine, 2,2'-(piperazine-1,4-diyl) diethanol, isophorone diisocyanate, castor oil, and acetic acid. These nanoparticles, identified as WPU 0.89 @LA, WPU 0.99 @LA, WPU 1.09 @LA, and WPU 1.19 @LA, underwent assessment for their pH-responsive release property and biocompatibility. Among these, WPU 0.99 @LA displayed superior pH-responsive release properties and biocompatibility towards Caco-2 and IPEC-J2 cells. In a mouse model, a dosage of 10 mg/kg/day WPU 0.99 @LA effectively reduced the conjugation of IncX4 plasmids carrying the mobile colistin resistance gene ( mcr-1 ) by more than 45.1-fold. In vivo toxicity assessment demonstrated that 10 mg/kg/day WPU 0.99 @LA maintains desirable biosafety and effectively preserves gut microbiota homeostasis. In conclusion, our study provides crucial proof-of-concept support, demonstrating that WPU 0.99 @LA holds significant potential in controlling the spread of antibiotic resistance within the mammalian intestine.
研究领域:
药理学
·
纳米技术
·
微生物学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2013
·Vol. 378
·期 1
·73-81
·
IF 2.329
Cai Xuan,Chen Xiaolian,Wang Xiaochun,Xu Congcong,Guo Qi,Zhu Lihui,Zhu Shuwen,Xu Jianxiong
A lpha-lipoic acid (LA) is considered to be a universal antioxidant. The intestine is very sensitive to a wide range of stressors for it exposed in a complex microenvironment that usually contained excess free radicals. The objective of this study was to evaluate the pre-protective effect of LA on intestinal epithelial cell injury induced by H 2 O 2 . In this research, IPEC-J2 cells were divided into three groups: the control group, the H 2 O 2 -treated group, and the LA pre-protective group. Cell viability, intracellular ROS, DNA damage integrity, and antioxidant enzyme activity of all groups were measured. Quantitative reverse transcription-PCR was used to determine the influence of oxidative stress and LA on the GH/IGF-1 axis in IPEC-J2 cells. The research selected 1 mM H 2 O 2 and 10 μg/ml as modeling concentration. The data indicated that H 2 O 2 can significantly increase the intracellular free radicals, leading to serious DNA damage and significantly reduce superoxide dismutase, glutathione peroxidase, catalase, and lipase activity. LA-protected IPEC-J2 cells against H 2 O 2 -induced injury by scavenging hydroxyl radical. In the current study, LA pre-protective group share a lower intracellular ROS and lower DNA damage compare to H 2 O 2 -treated group ( P < 0.01); and also, a higher lipase activity were detected in LA pre-protective group compare to H 2 O 2 -treated group ( P < 0.05). But the mechanism between oxidative stress, LA effect, and GH/IGF-1 axis is still unknown. The model used in the current study is also suitable for other feed additive screening.
研究领域:
营养学
·
细胞生物学
·
分子生物学
·
兽医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ANIMAL PHYSIOLOGY AND ANIMAL NUTRITION
·
2023
·
IF 2.7
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Ruixia Wu,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Inflammatory response induced by biological stress usually occurs in weaning piglets, it reduces the production performance of piglets and even causes death. Tert-butylhydroquinone (TBHQ) is a food additive that has the effect of anti-inflammation and anti-oxidation. However, there are few reports related to the protective mechanisms of TBHQ on lipopolysaccharide (LPS) induced injury in intestinal porcine epithelial (IPEC-J2) cells. Quantitative real-time polymerase chain reaction and western blot analysis, respectively, detected the mRNA levels and protein expressions related to pyroptosis, tight junction (TJ) protein and high-mobility group box 1/toll-like receptor 4/nuclear factor kappa-B (HMGB1/TLR4/NF-κB) axis. Localisation and expression of NOD-like receptor pyrin domain containing 3 (NLRP3), HMGB1 and P-NF-κB proteins detected by immunofluorescence. The results showed that TBHQ (12.5 and 25 μM) can increase cell activity and reduce intracellular lactate dehydrogenase (LDH) levels in a dose-dependent manner. LPS significantly decreases cell viability and increases the LDH level. However, pretreatment with TBHQ evidently increases cell viability and decreases the LDH level of IPEC-J2 cells. In addition, treatment with LPS decreased the mRNA level and protein expression of zonula occludens-1, occludin and claudin-1, and increased the mRNA level and protein expression of pyroptosis and HMGB1/TLR4/NF-κB axis. Interestingly, pretreatment with TBHQ increased the TJ protein expressions as well as decreased the mRNA level and protein expressions of pyroptosis and HMGB1/TLR4/NF-κB axis. Moreover, the results of immunofluorescence showed that TBHQ significantly reduced the expression of NLRP3, HMGB1 and P-NF-κB in LPS-induced injury of IPEC-J2 cells. Therefore, we come to the conclusion that TBHQ attenuates LPS-induced pyroptosis in IPEC-J2 cells through downregulation of the HMGB1/TLR4/NF-κB axis, TBHQ may become a potential feed additive for preventing inflammatory diarrhoea in piglets.
研究领域:
兽医学
·
细胞生物学
·
免疫学
·
动物营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Veterinary Science
·
2024
·
IF 2.6
Zhou Miao,Wu Zichen,Deng Donghua,Wang Bin,Zhou Xiaoling,Zhou Bingyu,Wang Chunping,Zeng Yan
Oxidative damage resulting from weaning stress significantly impacts the growth performance and health status of piglets. Taurine, a dietary antioxidant with diverse functions, was investigated in this study for its protective role against weaning stress-induced oxidative damage and its underlying mechanism. Forty 28-day-old male castrated weaned piglets were randomly assigned to four groups. The control group received the basal diet, while the experimental groups were fed the basal diet supplemented with 0.1, 0.2%, or 0.3% taurine over a 28-day period. In vitro, H2O2 was utilized to induce oxidative damage to the jejunal mucosa of piglets via IPEC-J2 cells. The results demonstrated that taurine supplementation reduced the incidence of diarrhea in piglets compared to that in the control group (p < 0.05); the addition of 0.2 and 0.3% taurine led to increased average daily gain and improved feed conversion efficiency in weaned piglets, showing a linear dose-response correlation (p < 0.05). Taurine supplementation at 0.2 and 0.3% enhanced the activities of serum CAT and GSH-Px while decreasing the levels of serum NO, XOD, GSSG, and MDA (p < 0.05). Moreover, it significantly elevated the levels of GSS, Trx, POD, complex I, mt-nd5, and mt-nd6, enhancing superoxide anion scavenging capacity and the hydroxyl-free scavenging rate in the livers of weaned piglets while reducing NO levels in the liver (p < 0.05). Additionally, 0.2 and 0.3% taurine supplementation decreased serum IL-6 levels and elevated the concentrations of IgA, IgG, and IL-10 in weaned piglets (p < 0.05). The levels of occludin, claudin, and ZO-1 in the jejunum mucosa of weaned piglets increased with 0.2 and 0.3% taurine supplementation (p < 0.05). In IPEC-J2 cells, pretreatment with 25 mM taurine for 24 h enhanced the activities of SOD and CAT; reduced the MDA content; upregulated the mRNA expression of various genes, including ZO-1, occludin, claudin-1, Nrf2, and HO-1; and reversed the oxidative damage induced by H2O2 exposure (p < 0.05). Overall, the findings suggest that the inclusion of 2 and 3% taurine in the diet can enhance growth performance, reduce diarrhea rates, ameliorate oxidative stress and inflammation, and promote intestinal barrier function in weaned piglets.
研究领域:
动物科学
·
营养学
·
生理学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2023
·
IF 11.2
Xueting Niu,Canying Hu,Shengwei Chen,Jiaying Wen,Xiaoxi Liu,Yanhong Yong,Zhichao Yu,Xingbin Ma,Chengpeng Li,Mohamad Warda,A.M. Abd El-Aty,Ravi Gooneratne,Xianghong Ju
Heat stress (HS) has a negative impact on animal health. A modified chitosan-gentamicin conjugate (CS-GT) was prepared to investigate its potential protective effects and mechanism of action on heat stress-induced intestinal mucosa injury in IPEC-J2 cells and mouse 3D intestinal organs in a mouse model. CS-GT significantly ( P < 0.01) reversed the decline in transmembrane resistance and increased the FITC-dextran permeability of the IPEC-J2 monolayer fusion epithelium caused by heat stress. Heat stress decreased the expression of the tight binding proteins occludin , claudin1, and claudin2. However, pretreatment with CS-GT significantly increased ( P < 0.01) the expression of these tight binding proteins. Mechanistically, CS-GT inhibited the activation of the TLR4/STAT6/MYLK signaling pathway induced by heat stress. Molecular docking showed that CS-GT can bind effectively with TLR4 . In conclusion, CS-GT alleviates heat stress-induced intestinal mucosal damage both in vitro and in vivo . This effect is mediated, at least partly, by the inhibition of the TLR4/STAT6/MYLK signaling pathway and upregulation of tight junction proteins. These findings suggest that CS-GT may have therapeutic potential in the prevention and treatment of heat stress-related intestinal injury.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Probiotics and Antimicrobial Proteins
·
2025
·
IF 4.4
Chen Fengming,Wu Shu,Wang Xiaoyu,Li Yinghui,He Binsheng,Fu Yafen,Huang Xingguo,Chen Jiayi
Reducing the negative impact of oxidative stress (OS) on weaned piglets is crucial for the further development of the pig industry. Our previous studies found that Lactobacillus delbrueckii (LAB) can alleviate OS and protect intestinal health by activating TLR2 and TLR4 expressions in weaned piglets. This research aimed to verify whether LAB can alleviate OS and intestinal barrier injuries in IPEC-J2 cells by activating TLR2 and TLR4. IPEC-J2 cells were first pretreated with 10 10 CFU/mL LAB for 12 h, and then were induced to OS by 0.8 mmol/L H 2 O 2 for another 12 h. The results showed that LAB significantly alleviated OS induced by H 2 O 2 , indicated by the downregulation of MDA ( P < 0.05), along with upregulation of GSH-Px, CAT, T-SOD, and T-AOC ( P < 0.05). Besides, LAB significantly alleviated intestinal barrier injuries induced by H 2 O 2 , indicated by the upregulation of Claudin-1, Occludin, and ZO-1 expressions. Subsequently, the IPEC-J2 cells were pretreated with inhibitors of TLR2 (TLR2-IN-C29) and TLR4 (MD2-TLR4-IN-1) in the absence of LAB for 12 h, and then treated with 0.8 mmol/L H 2 O 2 for another 12 h. The results showed that both inhibitors significantly prevented the protection effects of LAB on H 2 O 2 -induced OS, indicated by the downregulation of CAT, SOD1, HO-1, and GSH-Px1 expressions ( P < 0.05). Taken together, LAB treatment can alleviate OS and intestinal injuries induced by H 2 O 2 by activating TLR2 and TLR4 expressions in IPEC-J2 cells, thus providing novel theoretical support for LAB in the prevention and treatment of oxidative damage.
研究领域:
动物科学
·
微生物学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）