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CircRNA-IGLL1/miR-15a/RNF43 axis mediates ammonia-induced autophagy in broilers jejunum via Wnt/β-catenin pathway
2022
Wang, Yue | Wang, Shengchen | Jing, Hongyuan | Zhang, Tianyi | Song, Nuan | Xu, Shiwen
With the continued increase of global ammonia emission, the damage to human or animal caused by ammonia pollution has attracted wide attention. The noncoding RNAs have been reported to regulate a variety of biological processes under different environmental stimulation via ceRNA (competing endogenous RNA) networks. Autophagy is a hallmark of tissue damage from air pollution. However, the specific role of circular RNAs (circRNAs) in the injury of intestinal tissue caused by autophagy remains unclear. Here, we established 42-days old ammonia-exposed broiler models and observed that autophagy flux in broiler jejunum was activated under ammonia exposure. Meanwhile, a total of eight significantly dysregulated expressed circRNAs were obtained and a circRNAs-miRNAs-genes interaction networks were constructed by bioinformatics analysis. Furthermore, an axis named circRNA-IGLL1/miR-15a/RNF43 was predicted to participate in the excessive autophagy by targeting RNF43. The target relationship was proved by dual-luciferase reporter assay in vitro. Mechanistically, downregulated circRNA-IGLL1 could suppress the expression of RNF43 in ammonia-exposed jejunum and the Wnt/β-catenin pathway was activated. Inhibition of miR-15a reversed autophagy caused by downregulated circRNA-IGLL1. CircRNA-IGLL1 could competitively bind miR-15a to regulate RNF43 expression, thus modulating the occurrence of autophagy. Taken together, our results showed that circRNA-IGLL1/miR-15a/RNF43 axis is involved in ammonia-induced intestinal autophagy in broilers.
Mostrar más [+] Menos [-]Glyphosate exposure induces inflammatory responses in the small intestine and alters gut microbial composition in rats
2020
Tang, Qian | Tang, Juan | Ren, Xin | Li, Chunmei
Glyphosate is the most popular herbicide used worldwide. This study aimed to investigate the adverse effects of glyphosate on the small intestine and gut microbiota in rats. The rats were gavaged with 0, 5, 50, and 500 mg/kg of body weight glyphosate for 35 continuous days. The different segments of the small intestine were sampled to measure indicators of oxidative stress, ion concentrations and inflammatory responses, and fresh feces were collected for microbiota analysis. The results showed that glyphosate exposure decreased the ratio of villus height to crypt depth in the duodenum and jejunum. Decreased activity of antioxidant enzymes (T-SOD, GSH, GSH-Px) and elevated MDA content were observed in different segments of the small intestine. Furthermore, the concentrations of Fe, Cu, Zn and Mg were significantly decreased or increased. In addition, the mRNA expression levels of IL-1β, IL-6, TNF-α, MAPK3, NF-κB, and Caspase-3 were increased after glyphosate exposure. The 16 S rRNA gene sequencing results indicated that glyphosate exposure significantly increased α-diversity and altered bacterial composition. Glyphosate exposure significantly decreased the relative abundance of the phylum Firmicutes and the genus Lactobacillus, but several potentially pathogenic bacteria were enriched. In conclusion, this study provides important insight to reveal the negative influence of glyphosate exposure on the small intestine, and the altered microbial composition may play a vital role in the process.
Mostrar más [+] Menos [-]Synthesized chrysin-loaded nanoliposomes improves cadmium-induced toxicity in mice
2020
Beyrami, Mahsan | Karimi, Ehsan | Oskoueian, Ehsan
In this study, chrysin as a natural flavonoid was encapsulated in nanoliposomal structures, and the synthesized nanoliposome-loaded chrysin (NLC) was further characterized for its physical properties and cytoprotective effects in mice that received cadmium-containing water. The results showed that the synthesized NLC is possessed spherical structure with the size of 185.1 nm and negative surface charge of − 26 mV with a poly dispersity index of 0.26. The mice received cadmium (2 mg/kg body weight/day) through drinking water showed weight loss and decease in the feed intake significantly (p ≤ 0.05). The cadmium notably (p ≤ 0.05) increased the liver enzymes including aspartate aminotransferase, alanine transaminase, and alkaline phosphatase; altered the liver metal deposition (cadmium, copper, manganese, selenium, and zinc); and induced hepatic oxidative stress (inducible nitric oxide synthase, catalase, superoxide dismutase, and glutathione peroxidase genes) with no remarkable histopathological changes. Furthermore, the cadmium impaired the morphology of jejunum through reducing villus height and villus width and increasing the crypt depth. Providing NLC as a dietary supplement at the concentrations of 2.5 and 5 mg/kg mice body weight significantly (p ≤ 0.05) improved the feed intake and body weight gain, modulated the liver enzymes, and alleviated the hepatic oxidative stress. The NLC also improved the antioxidant mineral deposition in the liver and morphohistological structure of jejunum. Consequently, the NLC is suggested as a potential dietary supplement to alleviate the symptoms of cadmium-induced toxicity in mice.
Mostrar más [+] Menos [-]The gut-microbiota-testis axis mediated by the activation of the Nrf2 antioxidant pathway is related to prepuberal steroidogenesis disorders induced by di-(2-ethylhexyl) phthalate
2020
Zhao, Tian-Xin | Wei, Yue-Xin | Wang, Jun-Ke | Han, Lin-Dong | Sun, Mang | Wu, Yu-Hao | Shen, Lian-Ju | Long, Chun-Lan | Wu, Sheng-De | Wei, Guang Hui
Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer, which is known to be an environmental endocrine-disrupting chemical that can jeopardize the male reproductive system. Prepuberal exposure to DEHP leads to steroidogenesis disorders. However, the specific mechanism remains ambiguous. Therefore, Sprague Dawley (SD) rats underwent prepuberal DEHP exposure at a dose of 500 mg/kg per day through gavage. Additionally, the resulting testicular injury was evaluated to confirm the disturbed steroidogenesis. Changes in testicular histology, significant reduction of serum testosterone (P < 0.01) and luteinizing hormone (P < 0.001), and significantly decreased expressions of steroidogenic acute regulatory protein (P < 0.01) and 3-beta-hydroxysteroid dehydrogenase (P < 0.05) were found in DEHP-treated rats. DEHP exposure resulted in obvious intestinal damage and oxidative stress imbalance, primarily in the jejunum. Both the activation of the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway and alterations of microbiota profiles were observed in all three gut specimens, but were most notable in the jejunum. We hypothesize that the gut-microbiota-testis axis, which is mediated by the activation of the Nrf2 antioxidant pathway, could be involved in the dysfunction of prepuberal steroidogenesis induced by DEHP.
Mostrar más [+] Menos [-]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.
Mostrar más [+] Menos [-]Interplay between elemental imbalance-related PI3K/Akt/mTOR-regulated apoptosis and autophagy in arsenic (III)-induced jejunum toxicity of chicken
2018
Wang, Yu | Zhao, Hongjing | Shao, Yizhi | Liu, Juanjuan | Li, Jinglun | Xing, Mingwei
Arsenic trioxide (As₂O₃), the most toxic form of arsenic found in foodstuffs, is considered a carcinogen for human and animal. But many of the events that occur during its passage through the gastrointestinal tract are uncharted in birds. This study assesses the toxic effect on the jejunum of chicken which subchronically exposed to diets that contain As₂O₃ (0, 0.625, 1.25, 2.5 mg/kg body weight) for 90 days. Electron microscopy, TdT-mediated dUTP nick-end labeling (TUNEL), qPCR, and Western blot were performed. The results showed that mitochondrial fusion and apoptosis inhibiting genes had degressive trends, whereas mitochondrial fission and apoptosis activating genes presented heightened expressions in the treatment group compared with the control (P < 0.05). Subsequently, significant inhibition in PI3K/AKT/mTOR signaling was observed. Moreover, the expression of autophagy markers (LC3-II/LC3-I, Beclin-1) increased time and dose-dependently. Additionally, metabolic disorders of trace elements were detected evidenced by their significant decreases (aluminum, silicon, calcium, manganese, strontium, titanium, lithium, boron, cobalt, mercury, chromium) and increases (arsenic, cadmium, selenium, lead, nickel) on 90 days using inductively coupled plasma mass spectrometer (ICP-MS). It is possible that the changes of trace elements have a hand in the come on and development of arsenism. Taken together, we conjectured that, in chicken jejunum, arsenic led to redistribution of trace elements, promoting apoptosis via regulating mitochondrial dynamics, leading to autophagy through PI3K/AKT/mTOR signal pathways.
Mostrar más [+] Menos [-]Deciphering the ionic homeostasis, oxidative stress, apoptosis, and autophagy in chicken intestine under copper(II) stress
2018
Zhao, Hongjing | Wang, Yu | Shao, Yizhi | Liu, Juanjuan | Liu, Yanhua | Xing, Mingwei
As cofactors of several enzymatic, copper (Cu) participates in many essential metabolic processes. Also, as a heavy metal, it exhibits highly toxic to the organism if excessive. This study endeavored to detect the pathophysiological changes in the jejunum of chickens, which were insulted by CuSO₄ (300 mg/kg diet) for 90 days. Results showed metabolic disorders of trace elements evidenced by their significant downregulations (Na, Al, Li, B, Cr, Ni, Sn, Sb, Ba) and upregulations (Cu, Si, As, Cd, Se, and Tl) in 90 days. Simultaneously, increased TdT-mediated dUTP nick end labeling (TUNEL)-positive nuclei and distinct ultrastructural apoptotic features were observed. Meanwhile, in 30, 60, and 90 days, indicators of oxidative stress, apoptosis, autophagy, and mitochondrial dynamic were detected to uncover the molecular mechanism behind these pathological changes. The results showed that suppressed antioxidant ability was companied by increased mRNA and protein levels of proapoptosis and mitochondrial fission activating genes in the Cu group compared with chickens in the control group (P < 0.05). Moreover, the markers of autophagy long-chain 3 (LC3-II/LC3-I), Bcl-2-interacting protein (beclin-1), and autophagy-related gene (ATG4B and ATG5) displayed a time-dependent increase during 30, 60, and 90 days. We conjectured that subchronic copper poisoning, under the background of redistribution of trace elements, induced oxidative stress and cascaded apoptosis, autophagy, and mitochondrial disorder, which contributed to jejunotoxicity in chicken. Collectively, our study provides a basic assessment of subchronic Cu exposure on poultry, voicing concerns about copper pollution by anthropogenic activities.
Mostrar más [+] Menos [-]Impact of thyme powder (Thymus vulgaris L.) supplementation on gene expression profiles of cytokines and economic efficiency of broiler diets
2017
Hassan, Fardos A. M. | Awad, Ashraf
This study was conducted in an attempt to evaluate the impact of thyme powder supplementation on broiler diets with respect to cytokine and mucin2 gene expressions. It was also our aim to evaluate the growth performance, blood biochemical and hematological profiles, and economic efficiency of the diet. A total of 120 1-day old chicks (Cobb 500) were divided into four groups on the basis of the diet. One group received a basal diet (control) while the others received a basal diet supplemented with 2, 5, or 8 g/kg of thyme powder. At 42 days of age, the chickens were weighed and euthanized, and then blood and tissue samples were collected for the purpose of analysis. Results obtained clearly indicated that thyme supplementation of the diet, especially at 5 g/kg, resulted in a significant increase in body weight and caused the increased body weight gain and feed intake (P ˂ 0.05) as well as augmented WBC and lymphocyte count and IgG and NO levels (P ˂ 0.001). The economic evaluation showed that birds fed on 8 g/kg thyme yielded the lowest net revenue and highest feed cost to produce 1 kg of live weight compared to the other treatments, while birds fed on 2 and 5 g/kg thyme did not differ significantly from values obtained for the controls. The lipid profile of the broilers was affected by thyme supplementation at 2 and 5 g/kg as represented by a significant decrease in serum cholesterol levels as well as low density lipoprotein levels, which is known to be associated with a corresponding increase in high-density lipoprotein (P ˂ 0.001). Furthermore, supplementation of thyme downregulated the pro-inflammatory mediators and increased the expression of mucin2 mRNA in the jejunum of chickens. It can be concluded that thyme supplementation in the diet of broilers at 5 g/kg has the potential to favorably influence productive performance via an improvement in the immune status of the broiler.
Mostrar más [+] Menos [-]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.
Mostrar más [+] Menos [-]Anticoccidial and antioxidant effects of plants derived polyphenol in broilers exposed to induced coccidiosis
2019
Alhotan, Rashed A. | Abudabos, Alaeldein
The comparative anticoccidial effects of herbal products with a standard synthetic anticoccidial drug on the production performance, intestinal histology, and some blood biochemical parameters in broilers exposed to experimental coccidiosis was investigated. One-day-old broiler chicks (n = 336) were randomly distributed into six groups. One group served as a control, the second was treated with the coccidial infection, the third was treated with synthetic anticoccidial drug (Elancoban), the fourth group was treated with an herbal product (Cozante), the fifth group of birds was treated with Norponin, and the sixth group was treated with Emanox. The results indicated that BWG, BW, FCR, and PEF decreased significantly (P < 0.05) in the positive control. Body weight gain, BW, and PEF were significantly (P < 0.01) high in Elancoban-treated birds. On day 25, lesion score was significantly (P < 0.01) low in duodenum, jejunum, and ceca in Elancoban-treated birds control. On day 30, lesion score was significantly (P < 0.05) low in Emanox-treated birds as compared with the positive control. Albumin concentration was significantly (P < 0.01) low in Emanox while glucose concentration was significantly (P < 0.01) high in all the treated groups compared with the positive control birds. The total antioxidant capacity was significantly (P < 0.05) high in Emanox on day 15 and 30 as compared with the positive control. The results showed that birds exposed to the natural anticoccidial products showed improved villi and total antioxidant capacity. We concluded that herbal products performed better than the positive control group.
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