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Developmental exposure to polychlorinated biphenyls (PCBs) in the maternal diet causes host-microbe defects in weanling offspring mice
2019
Rude, Kavi M. | Pusceddu, Matteo M. | Keogh, Ciara E. | Sladek, Jessica A. | Rabasa, Gonzalo | Miller, Elaine N. | Sethi, Sunjay | Keil, Kimberly P. | Pessah, Isaac N. | Lein, Pamela J. | Gareau, Mélanie G.
The gut microbiota is important for maintaining homeostasis of the host. Gut microbes represent the initial site for toxicant processing following dietary exposures to environmental contaminants. The diet is the primary route of exposure to polychlorinated biphenyls (PCBs), which are absorbed via the gut, and subsequently interfere with neurodevelopment and behavior. Developmental exposures to PCBs have been linked to increased risk of neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), which are also associated with a high prevalence of gastrointestinal (GI) distress and intestinal dysbiosis. We hypothesized that developmental PCB exposure impacts colonization of the gut microbiota, resulting in GI pathophysiology, in a genetically susceptible host. Mouse dams expressing two heritable human mutations (double mutants [DM]) that result in abnormal Ca²⁺ dynamics and produce behavioral deficits (gain of function mutation in the ryanodine receptor 1 [T4826I-RYR1] and a human CGG repeat expansion [170–200 CGG repeats] in the fragile X mental retardation gene 1 [FMR1 premutation]). DM and congenic wild type (WT) controls were exposed to PCBs (0–6 mg/kg/d) in the diet starting 2 weeks before gestation and continuing through postnatal day 21 (P21). Intestinal physiology (Ussing chambers), inflammation (qPCR) and gut microbiome (16S sequencing) studies were performed in offspring mice (P28–P30). Developmental exposure to PCBs in the maternal diet caused significant mucosal barrier defects in ileum and colon (increased secretory state and tight junction permeability) of juvenile DM mice. Furthermore, PCB exposure increased the intestinal inflammatory profile (Il6, Il1β, and Il22), and resulted in dysbiosis of the gut microbiota, including altered β-diversity, in juvenile DM mice developmentally exposed to 1 mg/kg/d PCBs when compared to WT controls. Collectively, these findings demonstrate a novel interaction between PCB exposure and the gut microbiota in a genetically susceptible host that provide novel insight into environmental risk factors for neurodevelopmental disorders.
Afficher plus [+] Moins [-]Exposure to hexafluoropropylene oxide dimer acid (HFPO-DA) disturbs the gut barrier function and gut microbiota in mice
2021
Xie, Xiaoxian | Zhou, Jiafeng | Hu, Luting | Shu, Ruonan | Zhang, Mengya | Xiong, Ze | Wu, Fengchun | Fu, Zhengwei
Hexafluoropropylene oxide dimer acid (HFPO-DA) is the substitute for perfluoro octanoic acid (PFOA), and recently it has been detected in environmental water samples worldwide and has multiple toxicities. However, whether it will affect the intestines and gut microbiota remains unclear. In this study, in order to evaluate the gut toxicity of HFPO-DA in mammals, male mice were orally exposed to 0, 2, 20, 200 μg/L HFPO-DA, respectively, for 6 weeks. Our results showed that HFPO-DA exposure caused colonic inflammation which was coupled with increased TNF-α levels in serum and increased mRNA expression levels of TNF-α, p65, TLR4, MCP-1 of the colon in mice after exposure to 200 μg/L HFPO-DA. We also found that HFPO-DA exposure induced the decreased mRNA expression levels and protein levels of MUC2 and ZO-1, which means the dysfunction of gut barrier in the colon. In the ileum, we found that HFPO-DA exposure induced the increased mRNA expression levels of various inflammatory factors, but no obvious changes was found to barrier function. Additionally, HFPO-DA exposure caused the imbalance of cecal gut microbiota and changes of cecal microbiota diversity. Taken together, all these results indicate the potential gut toxicity of HFPO-DA and is perceived as a major problem of health risk that affects the inflammation, gut barrier dysfunction, and gut microbiota disturbance in mammals.
Afficher plus [+] Moins [-]Subchronic exposure of environmentally relevant concentrations of F-53B in mice resulted in gut barrier dysfunction and colonic inflammation in a sex-independent manner
2019
Pan, Zihong | Yuan, Xianling | Tu, Wenqing | Fu, Zhengwei | Jin, Yuanxiang
F-53B (6:2 chlorinated polyfluorinated ether sulfonate) is currently recognized as a safe alternative to long-chain PFASs in China. However, an increasing number of studies have recently authenticated its biotoxicological effects. In this study, for evaluating the gut toxicity of F-53B in mammals, both female and male mice were orally exposed to 0, 1, 3, or 10 μg/L F-53B for 10 weeks. Our results showed that F-53B significantly accumulated in the colon, ileum and serum when exposed to 10 μg/L F-53B for 10 weeks. F-53B exposure not only increased the transcriptional levels of ion transport-related genes but could also interact with the CFTR protein directly. Interestingly, subchronic F-53B exposure also increased the transcription of mucus secretion-related genes, but the protein level of Muc2 decreased after F-53B exposure, indicating that there was a compensatory phenomenon after mucus barrier injury. Furthermore, F-53B exposure also induced colonic inflammation associated with gut microbiota dysbiosis in the colon. Taken together, our results indicated that the potential gut toxicity of F-53B and almost all of the changed parameters were significantly affected in both female and male mice, suggesting that F-53B could disturb the gut barrier without sex dependence in mice.
Afficher plus [+] Moins [-]The effectiveness of vitamin C on quinalphos ileal toxicity: a study of histological, ultrastructural, and oxidative stress markers
2022
Zaki, Mohamed Samir Ahmed | El-kott, Attalla F. | AlGwaiz, Hussah I. M. | Sideeg, Abulqasim M. | Andarawi, Mohamed | Eid, Refaat A.
There is a significant hazard of human exposure to the organophosphates which is a constant threat, and they are responsible for numerous cases of poisoning and mammalian toxicity annually in non-target wildlife. The antioxidants, including the vitamin C (Vit C), have a protective effect on some organophosphorus compounds-induced organ damage. Quinalphos (QP) is one of these compounds. The investigation’s objective is to see if there was any effect of QP on the rat ileum which could be rectified by using Vit C. Three groups of 24 animals were created. As a control, the first group was given pure water. Second group subjected to oral gavages of QPs. Third group rats were given oral gavages of Vit C plus QPs for 10 days. The reaction of ileal enterocytes to food-borne QPs was marked by poorly organized microvilli, numerous vacuoles within them, disrupted nuclei with chromatin margination, disoriented mitochondria, and an expanded intercellular space. The absorptive columnar cell illustrated many vacuoles inside with herniation of microvilli, and normal goblet cells were also seen. Many Paneth cells towards the lumen of intestinal gland contained secretory granules of different sizes and shapes. The histological architecture of the ileal mucosa in the QP plus Vit C group was found to be close to those of healthy controls. The outcomes of this study suggest that administering Vit C in rats treated with QPs protects them from ill dysfunction caused by QP.
Afficher plus [+] Moins [-]Cadmium induces apoptosis and autophagy in swine small intestine by downregulating the PI3K/Akt pathway
2022
Zhang, Haoran | Huang, Jiaqiang | Yang, Jie | Cai, Jingzeng | Liu, Qi | Zhang, Xintong | Bao, Jun | Zhang, Ziwei
Cadmium (Cd) is an environmental contaminant, which is potentially toxic. It is well known that Cd can accumulate in the liver and kidney and cause serious damage. However, few studies have investigated the mechanism of intestinal damage induced by Cd in swine. Here, we established Cd poisoning models in vivo and in vitro to explore the mechanism of intestinal injury induced by Cd in swine. The morphology of intestinal tissue cells was observed by TUNEL staining and electron microscopy, and the morphology of IPEC-J2 cells was observed by flow cytometry, Hoechst staining, and MDC staining. Cell morphological observations revealed that Cd treatment induced ileal apoptosis and autophagy. The effects of Cd on the PI3K/Akt pathway, as well as on apoptosis and autophagy-related protein expression in intestinal cells, were analyzed by western blot (WB) and the expression of mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The results showed that Cd induced autophagy by increasing the levels of autophagy markers Beclin1, Autophagy-associated gene 5 (ATG5), Autophagy-associated gene 16 (ATG16), and Microtubule-associated protein light chains 3–2 (LC3-II), and by reducing the expression levels of Mechanistic target of rapamycin kinase (mTOR) and Microtubule-associated protein light chains 3–1 (LC3-I). Cell apoptosis was induced by increasing the expression of apoptosis markers Bcl-2 associated X protein (Bax), Cysteinyl aspartate specific proteinase 9 (Caspase9), cleaved Caspase9, Cysteinyl aspartate specific proteinase 3 (Caspase3), and cleaved Caspase3, and by reducing the expression of B cell lymphoma/leukemia 2 (Bcl-2). At the same time, Cd decreased the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and their phosphorylation. We treated IPEC-J2 cells with the PI3K activator 740Y-P and analyzed the morphological changes as well as autophagy and apoptosis-related gene expression. The results showed that 740Y-P could reduce apoptosis and autophagy induced by Cd. In conclusion, our findings suggest that Cd induces intestinal apoptosis and autophagy in swine by inactivating the PI3K/Akt signaling pathway.
Afficher plus [+] Moins [-]Protective effects of dietary betaine on intestinal barrier function and cecal microbial community in indigenous broiler chickens exposed to high temperature environment
2021
Liu, Wen-Chao | Guo, Yan | An, Li-Long | Zhao, Zhi-Hui
High temperature environment causes reduction in productivity in broilers by disrupting the intestinal barrier function. This study aimed to investigate the protective effects of dietary betaine on intestinal barrier function and cecal microbial community in indigenous broilers (Huaixiang chickens) exposed to high temperature environment. A total of 144 5-week-old male broilers (average initial body weight of 401.62 ± 9.51 g) were randomly allocated to three treatments for 10 weeks feeding trial; each treatment contained six replicates with eight birds per replicate. The three treatments included normal temperature control group (NT, fed basal diet, 26 ± 1 °C), high temperature control group (HT, fed basal diet, 32 ± 1 °C for 8 h/day), and HT group supplemented 1000 mg/kg betaine (HTB). The results showed that high temperature environment reduced the Occludin, Claudin-4, and ZO-1 expressions in duodenal mucosa (P < 0.05). Dietary betaine improved the Claudin-4 and ZO-1 expressions of duodenal mucosa (P < 0.05). In jejunal mucosa, HT group had lower Occludin, Claudin-1, Claudin-4, and ZO-1 expressions than NT group (P < 0.05). Compared with HT group, HTB group had higher Occludin and ZO-1 expression (P < 0.05). In ileal mucosa, the relative mRNA expression of ZO-1 in HT group was lower than those in NT group (P < 0.01), and dietary betaine (HTB group) improved ZO-1 expression compared with HT group (P < 0.05). Based on the results of 16S rRNA sequencing, the enriched and dominant microbials in NT group are Epsilonbacteraeota, Bacteroidetes, and Gammaproteobacterial, the enriched and dominant microbial in HT group is Muribaculaceae, and Firmicutes is the enriched and dominant microbial in HTB group. Taken together, the findings revealed that dietary betaine improved the intestinal barrier function and cecal microbial community in indigenous broilers under high ambient temperature.
Afficher plus [+] Moins [-]Improving growth performance and health status of meat-type quail by supplementing the diet with black cumin cold-pressed oil as a natural alternative for antibiotics
2018
Abd El-Hack, MohamedE. | Mahgoub, SamirA. | Hussein, MohamedM. A. | Saadeldin, IslamM.
Using antibiotics in poultry diets as growth promoters was reported to have harmful effects on consumers, so the current study was done to monitor the impact of dietary supplementation of antimicrobial black cumin oil (BCO) on carcass traits, growth performance, biochemical components, and ileal microbial populations of growing Japanese quails. Three hundred growing Japanese quails were used with three different treatments (0, 0.50, and 1.0 g BCO/g diet). Birds fed diet supplemented with 0.5 g BCO/kg diet showed significant increase in body weight comparing with the control and other treatment group. The daily feed intake and feed conversion ratio were significantly increased side by side with increasing BCO level in the diet. The majority of carcass characteristics were maximized by supplementing the quail diet with 0.5 g BCO/kg. Moreover, liver functions, anti-oxidative capacity, lipid profile and anabolic hormones showed significant improvement in BCO-treated diets in a dose-dependent manner. The BCO showed highest antibacterial effect against Escherichia coli and Salmonella enterica. The ileal bacterial populations, i.e., total bacterial count (TBC), coliform, Salmonella species, and Escherichia coli were decreased in birds supplemented with BCO 0.5 and 1.0 BCO g/kg compared with the control diet. Based on the aforementioned results, conclusion could be drawn that supplementing quail with BCO in their diet could improve productive performance traits and enhance health aspect of the birds.
Afficher plus [+] Moins [-]Disruption of cytochrome P450 enzymes in the liver and small intestine in chicken embryos in ovo exposed to glyphosate
2020
Fathi, Mohamed Ahmed | Han, Guofeng | Kang, Ruifen | Shen, Dan | Shen, Jiakun | Li, Chunmei
Glyphosate is the active component of several commercial formulations as in Roundup®. The present study was investigated the toxic effects of pure glyphosate or Roundup® on the liver and small intestine of chick embryos. On day 6, a total of 180 fertile eggs injected with deionized water (control group), 10 mg pure glyphosate, or 10 mg of the active ingredient glyphosate in Roundup®/kg egg mass. The results showed an increase in relative weights of the liver in embryos that treated with Roundup®. Furthermore, oxidative stress was observed in the embryos treated with glyphosate or Roundup®, increased total superoxide dismutase, and content of malondialdehyde in the liver and intestine; moreover, decrease of glutathione peroxidase in the liver with increased in the intestine compared with the control. Besides, glutamic-pyruvic transaminase was increased in Roundup® group compared with other groups. Moreover, histopathological alterations in the liver and intestine tissues were observed in treated groups. Suppression of hepatic CYP1A2, CYP1A4, CYP1B1, and MDR1 mRNA expression after exposed to Roundup®. Furthermore, inhibition of CYP1A4 in the duodenum, CYP1A4, and MRP2 in the jejunum in embryos exposed to glyphosate or Roundup®. In addition, glyphosate treatment caused an increase of CYP3A5, CYP1C1, and IFNY mRNA expression in the jejunum and CYP1A2 expression in the ileum, while IFN-Y gene increase in embryos treated with Roundup®. In conclusion, in ovo exposure to glyphosate caused histopathological alterations and induced oxidative stress in the liver and small intestines. Moreover, the expression of cytochrome P450, MDR1, and MRP2 transporters was also modulated in the liver and small intestines for chick embryos.
Afficher plus [+] Moins [-]Vitamin E alleviates phoxim-induced toxic effects on intestinal oxidative stress, barrier function, and morphological changes in rats
2018
Sun, Yuecheng | Zhang, Jing | Song, Wentao | Shan, Anshan
Phoxim is an organic phosphorus pesticide that remains easily in the environment, such as human food and animal feed. The objective of this study was to explore the effect of vitamin E on phoxim-induced oxidative stress in the intestinal tissues of Sprague-Dawley (SD) rats. Forty-eight Sprague-Dawley rats were randomly assigned to a control group and three treatment groups: treatment group 1 (phoxim: 20 mg/kg·BW), treatment group 2 (phoxim: 180 mg/kg·BW), and treatment 3 (vitamin E + phoxim: 200 mg/kg·BW + 180 mg/kg·BW). Phoxim was given by gavage administration once a day for 28 days. The results showed that phoxim significantly reduced jejunum villus height in rats (P < 0.05), and decreased the mRNA expression of junction protein genes of rats, including Occlidin and Claudin-4 (P < 0.05). Phoxim reduced GSH content and T-AOC level in the intestinal mucosa (P < 0.05). The mRNA expression levels of oxidative stress-related genes (Nrf2 and GPx2) were decreased. The mRNA expression of SOD was significantly increased. In addition, phoxim increased the level of interleukin-6 (IL-6) in jejunum mucosa and significantly reduced the level of IL-8 in ileum mucosas, while significantly increased TNF-α secretion. The mRNA expression levels of IL-1β, IL-6, and IL-8 were significantly decreased, and mRNA expression of TNF-α was significantly increased (P < 0.05). Phoxim also increased the DNA expression of total cecal bacteria and Escherichia coli, inhibited the DNA expression of Lactobacillus and destroyed the intestinal barrier. Two hundred milligrams per kilogram BW vitamin E reduced the effect of phoxim on intestinal structure, alleviated the oxidative stress in intestinal tissue, and decreased the level of TNF-α. The mRNA expressions of antioxidative stress genes (SOD and GPx2) were significantly increased. The DNA expression level of Lactobacillus was significantly increased. In conclusion, vitamin E helped reduce the toxicity of organophosphate pesticides, such as phoxim on rat intestinal tissue.
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