Zinc glycinate alleviates LPS-induced inflammation and intestinal barrier disruption in chicken embryos by regulating zinc homeostasis and TLR4/NF-κB pathway.
Xiao, Chuanpi; Comer, Luke; Pan, Xueet al.
2024 • In Ecotoxicology and Environmental Safety, 272, p. 116111
Chicken embryos; Immune challenge; In ovo feeding; Lipopolysaccharide; Zinc; NF-kappa B; Lipopolysaccharides; Toll-Like Receptor 4; zinc glycinate; Saline Solution; Glycine; Chick Embryo; Animals; Toll-Like Receptor 4/metabolism; Chickens/metabolism; Saline Solution/toxicity; Inflammation/chemically induced; Inflammation/veterinary; Homeostasis; Zinc/toxicity; Glycine/analogs & derivatives; NF-kappa B/genetics; NF-kappa B/metabolism; Lipopolysaccharides/toxicity; Health, Toxicology and Mutagenesis; Public Health, Environmental and Occupational Health; Pollution; General Medicine
Abstract :
[en] The effect of an immune challenge induced by a lipopolysaccharide (LPS) exposure on systemic zinc homeostasis and the modulation of zinc glycinate (Zn-Gly) was investigated using a chicken embryo model. 160 Arbor Acres broiler fertilized eggs were randomly divided into 4 groups: CON (control group, injected with saline), LPS (LPS group, injected with 32 µg of LPS saline solution), Zn-Gly (zinc glycinate group, injected with 80 µg of zinc glycinate saline solution) and Zn-Gly+LPS (zinc glycinate and LPS group, injected with the same content of zinc glycinate and LPS saline solution). Each treatment consisted of eight replicates of five eggs each. An in ovo feeding procedure was performed at 17.5 embryonic day and samples were collected after 12 hours. The results showed that Zn-Gly attenuated the effects of LPS challenge-induced upregulation of pro-inflammatory factor interleukin 1β (IL-1β) level (P =0.003). The LPS challenge mediated zinc transporter proteins and metallothionein (MT) to regulate systemic zinc homeostasis, with increased expression of the jejunum zinc export gene zinc transporter protein 1 (ZnT-1) and elevated expression of the import genes divalent metal transporter 1 (DMT1), Zrt- and Irt-like protein 3 (Zip3), Zip8 and Zip14 (P < 0.05). A similar trend could be observed for the zinc transporter genes in the liver, which for ZnT-1 mitigated by Zn-Gly supplementation (P =0.01). Liver MT gene expression was downregulated in response to the LPS challenge (P =0.004). These alterations caused by LPS resulted in decreased serum and liver zinc levels and increased small intestinal, muscle and tibial zinc levels. Zn-Gly reversed the elevated expression of the liver zinc finger protein A20 induced by the LPS challenge (P =0.025), while Zn-Gly reduced the gene expression of the pro-inflammatory factors IL-1β and IL-6, decreased toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) (P < 0.05). Zn-Gly also alleviated the LPS-induced downregulation of the intestinal barrier gene Claudin-1. Thus, LPS exposure prompted the mobilization of zinc transporter proteins and MT to perform the remodeling of systemic zinc homeostasis, Zn-Gly participated in the regulation of zinc homeostasis and inhibited the production of pro-inflammatory factors through the TLR4/NF-κB pathway, attenuating the inflammatory response and intestinal barrier damage caused by an immune challenge.
Disciplines :
Agriculture & agronomy
Author, co-author :
Xiao, Chuanpi ; Université de Liège - ULiège > TERRA Research Centre
Comer, Luke; Nutrition and Animal Microbiota Ecosystems lab, Department of Biosystems, KU Leuven, Leuven, Belgium
Pan, Xue; Key Laboratory of Efficient Utilization of Non-grain Feed Resources, Department of Animal Science, Shandong Agricultural University, Taian, Shandong, China
Everaert, Nadia ; Université de Liège - ULiège > TERRA Research Centre > Animal Sciences (AS) ; Nutrition and Animal Microbiota Ecosystems lab, Department of Biosystems, KU Leuven, Leuven, Belgium
Schroyen, Martine ; Université de Liège - ULiège > Département GxABT > Animal Sciences (AS)
Song, Zhigang; Key Laboratory of Efficient Utilization of Non-grain Feed Resources, Department of Animal Science, Shandong Agricultural University, Taian, Shandong, China. Electronic address: zhigangs@sdau.edu.cn
Language :
English
Title :
Zinc glycinate alleviates LPS-induced inflammation and intestinal barrier disruption in chicken embryos by regulating zinc homeostasis and TLR4/NF-κB pathway.
Al-Hakeim, H.K., Al-Rubaye, H.T., Al-Hadrawi, D.S., Almulla, A.F., Maes, M., Long-COVID post-viral chronic fatigue and affective symptoms are associated with oxidative damage, lowered antioxidant defenses and inflammation: a proof of concept and mechanism study. Mol. Psychiatry 28 (2023), 564–578.
Arab, J.P., Martin-Mateos, R.M., Shah, V.H., Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg. Hepatol. Int. 12 (2018), 24–33.
Bavananthasivam, J., Alkie, T.N., Matsuyama-Kato, A., Hodgins, D.C., Sharif, S., Characterization of innate responses induced by in ovo administration of encapsulated and free forms of ligands of Toll-like receptor 4 and 21 in chicken embryos. Res. Vet. Sci. 125 (2019), 405–415.
Borkowski, B.J., Cheema, Y., Shahbaz, A.U., Bhattacharya, S.K., Weber, K.T., Cation dyshomeostasis and cardiomyocyte necrosis: the Fleckenstein hypothesis revisited. Eur. Heart J. 32 (2011), 1846–1853.
Camilleri, M., Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 68 (2019), 1516–1526.
Chen, S., Liu, H., Li, Z., Tang, J., Huang, B., Zhi, F., Zhao, X., Epithelial PBLD attenuates intestinal inflammatory response and improves intestinal barrier function by inhibiting NF-κB signaling. Cell Death Dis., 12, 2021, 563.
Chen, G.H., Lv, W., Xu, Y.H., Wei, X.L., Xu, Y.C., Luo, Z., Functional analysis of MTF-1 and MT promoters and their transcriptional response to zinc (Zn) and copper (Cu) in yellow catfish Pelteobagrus fulvidraco. Chemosphere, 246, 2020, 125792.
Chua, J.S., Cowley, C.J., Manavis, J., Rofe, A.M., Coyle, P., Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice. Brain Behav. Immun. 26 (2012), 326–336.
Ciesielska, A., Matyjek, M., Kwiatkowska, K., TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling. Cell Mol. Life Sci. 78 (2021), 1233–1261.
Das, Q., Shay, J., Gauthier, M., Yin, X., Hasted, T.L., Ross, K., Julien, C., Yacini, H., Kennes, Y.M., Warriner, K., Marcone, M.F., Diarra, M.S., Effects of vaccination against coccidiosis on gut microbiota and immunity in broiler fed bacitracin and berry pomace. Front. Immunol., 12, 2021, 621803.
Doyle, S.L., O'Neill, L.A., Toll-like receptors: from the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem. Pharm. 72 (2006), 1102–1113.
Endo, K., Liu, Y., Ube, H., Nagata, K., Shionoya, M., Asymmetric construction of tetrahedral chiral zinc with high configurational stability and catalytic activity. Nat. Commun., 11, 2020, 6263.
Farhadi Javid, S., Moravej, H., Ghaffarzadeh, M., Esfahani, M.B., Comparison of zinc sulfate and zinc threonine based on zn bioavailability and performance of broiler chicks. Biol. Trace Elem. Res. 199 (2021), 2303–2311.
Forman, H.J., Zhang, H., Targeting oxidative stress in disease: promise and limitations of antioxidant therapy. Nat. Rev. Drug Discov. 20 (2021), 689–709.
Hennigar, S.R., Olson, C.I., Kelley, A.M., McClung, J.P., Slc39a4 in the small intestine predicts zinc absorption and utilization: a comprehensive analysis of zinc transporter expression in response to diets of varied zinc content in young mice. J. Nutr. Biochem., 101, 2022, 108927.
He, B., Bortoluzzi, C., King, W.D., Graugnard, D., Dawson, K.A., Applegate, T.J., Zinc source influences the gene expression of zinc transporters in jejunum and cecal tonsils during broiler challenge with Eimeria maxima and Clostridium perfringens. Poult. Sci. 98 (2019), 1146–1152.
Van Hoeck, V., Sonawane, M., Gonzalez Sanchez, A.L., Van Dosselaer, I., Buyens, C., Morisset, D., Chromium propionate improves performance and carcass traits in broilers. Anim. Nutr. 6 (2020), 480–487.
Hübner, C., Haase, H., Interactions of zinc- and redox-signaling pathways. Redox Biol., 41, 2021, 101916.
Izadparast, F., Riahi-Zajani, B., Yarmohammadi, F., Hayes, A.W., Karimi, G., Protective effect of berberine against LPS-induced injury in the intestine: a review. Cell Cycle 21 (2022), 2365–2378.
Jarosz, M., Olbert, M., Wyszogrodzka, G., Młyniec, K., Librowski, T., Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-κB signaling. Inflammopharmacology 25 (2017), 11–24.
Jia, R., Song, Z., Lin, J., Li, Z., Shan, G., Huang, C., Gawky modulates MTF-1-mediated transcription activation and metal discrimination. Nucleic Acids Res. 49 (2021), 6296–6314.
Kadam, M.M., Barekatain, M.R., Bhanja, S.K., Iji, P.A., Prospects of in ovo feeding and nutrient supplementation for poultry: the science and commercial applications–a review. J. Sci. Food Agric. 93 (2013), 3654–3661.
Kambe, T., Tsuji, T., Hashimoto, A., Itsumura, N., The physiological, biochemical, and molecular roles of zinc transporters in zinc homeostasis and metabolism. Physiol. Rev. 95 (2015), 749–784.
Kim, J., Lee, J., Ryu, M.S., Cellular Zinc Deficiency Impairs Heme Biosynthesis in Developing Erythroid Progenitors. Nutrients, 15, 2023.
Kirsten, T.B., Queiroz-Hazarbassanov, N., Bernardi, M.M., Felicio, L.F., Prenatal zinc prevents communication impairments and BDNF disturbance in a rat model of autism induced by prenatal lipopolysaccharide exposure. Life Sci. 130 (2015), 12–17.
Kong, L., Cai, Y., Pan, X., Xiao, C., Song, Z., Glycerol monolaurate improves intestinal morphology and antioxidant status by suppressing inflammatory responses and nuclear factor kappa-B signaling in lipopolysaccharide-exposed chicken embryos. Anim. Nutr. 15 (2023), 297–306.
Kong, L., Wang, Z., Xiao, C., Zhu, Q., Song, Z., Glycerol monolaurate attenuated immunological stress and intestinal mucosal injury by regulating the gut microbiota and activating AMPK/Nrf2 signaling pathway in lipopolysaccharide-challenged broilers. Anim. Nutr. 10 (2022), 347–359.
Lauridsen, C., From oxidative stress to inflammation: redox balance and immune system. Poult. Sci. 98 (2019), 4240–4246.
Liao, M.T., Wu, C.C., Wu, S.V., Lee, M.C., Hu, W.C., Tsai, K.W., Yang, C.H., Lu, C.L., Chiu, S.K., Lu, K.C., Resveratrol as an Adjunctive Therapy for Excessive Oxidative Stress in Aging COVID-19 Patients. Antioxid. (Basel), 10, 2021.
Liuzzi, J.P., Lichten, L.A., Rivera, S., Blanchard, R.K., Aydemir, T.B., Knutson, M.D., Ganz, T., Cousins, R.J., Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc. Natl. Acad. Sci. USA 102 (2005), 6843–6848.
Li, C., Guo, S., Gao, J., Guo, Y., Du, E., Lv, Z., Zhang, B., Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks. J. Nutr. Biochem. 26:2 (2015), 173–183.
Li, M.Y., Zhu, M., Linghu, E.Q., Feng, F., Zhu, B., Wu, C., Guo, M.Z., Interleukin-13 suppresses interleukin-10 via inhibiting A20 in peripheral B cells of patients with food allergy. Oncotarget 7 (2016), 79914–79924.
Maares, M., Haase, H., Zinc and immunity: an essential interrelation. Arch. Biochem. Biophys. 611 (2016), 58–65.
Meriwether, L.S., Humphrey, B.D., Peterson, D.G., Klasing, K.C., Koutsos, E.A., Lutein exposure, in ovo or in the diet, reduces parameters of inflammation in the liver and spleen laying-type chicks (Gallus gallus domesticus). J. Anim. Physiol. Anim. Nutr. (Berl. ) 94 (2010), e115–e122.
Nakamura, H., Sekiguchi, A., Ogawa, Y., Kawamura, T., Akai, R., Iwawaki, T., Makiguchi, T., Yokoo, S., Ishikawa, O., Motegi, S.I., Zinc deficiency exacerbates pressure ulcers by increasing oxidative stress and ATP in the skin. J. Dermatol. Sci. 95 (2019), 62–69.
Nguyen, H.T.T., Morgan, N., Roberts, J.R., Wu, S.B., Swick, R.A., Toghyani, M., Zinc hydroxychloride supplementation improves tibia bone development and intestinal health of broiler chickens. Poult. Sci., 100, 2021, 101254.
Nolin, E., Gans, S., Llamas, L., Bandyopadhyay, S., Brittain, S.M., Bernasconi-Elias, P., Carter, K.P., Loureiro, J.J., Thomas, J.R., Schirle, M., Yang, Y., Guo, N., Roma, G., Schuierer, S., Beibel, M., Lindeman, A., Sigoillot, F., Chen, A., Xie, K.X., Ho, S., Reece-Hoyes, J., Weihofen, W.A., Tyskiewicz, K., Hoepfner, D., McDonald, R.I., Guthrie, N., Dogra, A., Guo, H., Shao, J., Ding, J., Canham, S.M., Boynton, G., George, E.L., Kang, Z.B., Antczak, C., Porter, J.A., Wallace, O., Tallarico, J.A., Palmer, A.E., Jenkins, J.L., Jain, R.K., Bushell, S.M., Fryer, C.J., Discovery of a ZIP7 inhibitor from a Notch pathway screen. Nat. Chem. Biol. 15 (2019), 179–188.
Ogbuewu, I.P., Mbajiorgu, C.A., Potentials of dietary zinc supplementation in improving growth performance, health status, and meat quality of broiler chickens. Biol. Trace Elem. Res. 201 (2023), 1418–1431.
Oh, H.J., Park, Y.J., Cho, J.H., Song, M.H., Gu, B.H., Yun, W., Lee, J.H., An, J.S., Kim, Y.J., Lee, J.S., Kim, S., Kim, H., Kim, E.S., Lee, B.K., Kim, B.W., Kim, H.B., Cho, J.H., Kim, M.H., Changes in diarrhea score, nutrient digestibility, zinc utilization, intestinal immune profiles, and fecal microbiome in weaned piglets by different forms of zinc. Anim. (Basel), 11, 2021.
Pang, X., Miao, Z., Dong, Y., Cheng, H., Xin, X., Wu, Y., Han, M., Su, Y., Yuan, J., Shao, Y., Yan, L., Li, J., Dietary methionine restriction alleviates oxidative stress and inflammatory responses in lipopolysaccharide-challenged broilers at early age. Front Pharmacol., 14, 2023, 1120718.
Pan, Y., Lin, H., Jiao, H., Zhao, J., Wang, X., Effects of in ovo feeding of chlorogenic acid on antioxidant capacity of postnatal broilers. Front. Physiol., 14, 2023, 1091520.
Peace, C.G., O'Neill, L.A., The role of itaconate in host defense and inflammation. J. Clin. Invest., 132, 2022.
Pothuraju, R., Rachagani, S., Junker, W.M., Chaudhary, S., Saraswathi, V., Kaur, S., Batra, S.K., Pancreatic cancer associated with obesity and diabetes: an alternative approach for its targeting. J. Exp. Clin. Cancer Res., 37, 2018, 319.
Prasad, A.S., Discovery of human zinc deficiency: its impact on human health and disease. Adv. Nutr. 4 (2013), 176–190.
Qi, X., Ma, S., Liu, X., Wang, Y., Liu, Y., Gao, Y., Min, Y., Effects of the methionine hydroxyl analogue chelate zinc on antioxidant capacity and liver metabolism using (1)H NMR-based metabolomics in aged laying hens. Anim. (Basel), 9, 2019.
Retes, P.L., Clemente, A.H.S., Neves, D.G., Espósito, M., Makiyama, L., Alvarenga, R.R., Pereira, L.J., Zangeronimo, M.G., In ovo feeding of carbohydrates for broilers-a systematic review. J. Anim. Physiol. Anim. Nutr. (Berl. ) 102 (2018), 361–369.
Shembade, N., Harhaj, E.W., Regulation of NF-κB signaling by the A20 deubiquitinase. Cell Mol. Immunol. 9 (2012), 123–130.
Shimizu, S., Tei, R., Okamura, M., Takao, N., Nakamura, Y., Oguma, H., Maruyama, T., Takashima, H., Abe, M., Prevalence of zinc deficiency in japanese patients on peritoneal dialysis: comparative study in patients on hemodialysis. Nutrients, 12, 2020.
Stamoulis, I., Kouraklis, G., Theocharis, S., Zinc and the liver: an active interaction. Dig. Dis. Sci. 52 (2007), 1595–1612.
Summersgill, H., England, H., Lopez-Castejon, G., Lawrence, C.B., Luheshi, N.M., Pahle, J., Mendes, P., Brough, D., Zinc depletion regulates the processing and secretion of IL-1β. Cell Death Dis., 5, 2014, e1040.
Wu, A., Bai, S., Ding, X., Wang, J., Zeng, Q., Peng, H., Wu, B., Zhang, K., The systemic zinc homeostasis was modulated in broilers challenged by salmonella. Biol. Trace Elem. Res 196 (2020), 243–251.
Wu, X., Liu, S., Zhu, H., Ma, Z., Dai, X., Liu, W., Scavenging ROS to alleviate acute liver injury by ZnO-NiO@COOH. Adv. Sci. (Weinh. ), 9, 2022, e2103982.
Xiao, C., Kong, L., Pan, X., Zhu, Q., Song, Z., Everaert, N., High temperature-induced oxidative stress affects systemic zinc homeostasis in broilers by regulating zinc transporters and metallothionein in the liver and Jejunum. Oxid. Med Cell Longev., 2022, 2022, 1427335.
Xiong, T., Zheng, X., Zhang, K., Wu, H., Dong, Y., Zhou, F., Cheng, B., Li, L., Xu, W., Su, J., Huang, J., Jiang, Z., Li, B., Zhang, B., Lv, G., Chen, S., Ganluyin ameliorates DSS-induced ulcerative colitis by inhibiting the enteric-origin LPS/TLR4/NF-κB pathway. J. Ethnopharmacol., 289, 2022, 115001.
Yang, H., Hua, C., Yang, X., Fan, X., Song, H., Peng, L., Ci, X., Pterostilbene prevents LPS-induced early pulmonary fibrosis by suppressing oxidative stress, inflammation and apoptosis in vivo. Food Funct. 11 (2020), 4471–4484.
