Abstract
Sepsis is a life-threatening organ dysfunction caused by the dysregulated response of the host to an infection, and treatments are limited. Recently, a novel selenium source, selenium-enriched Cardamine violifolia (SEC) has attracted much attention due to its anti-inflammatory and antioxidant properties, but little is known about its role in the treatment of sepsis. Here, we found that SEC alleviated LPS-induced intestinal damage, as indicated by improved intestinal morphology, and increased disaccharidase activity and tight junction protein expression. Moreover, SEC ameliorated the LPS-induced release of pro-inflammatory cytokines, as indicated by decreased IL-6 level in the plasma and jejunum. Moreover, SEC improved intestinal antioxidant functions by regulating oxidative stress indicators and selenoproteins. In vitro, TNF-α-challenged IPEC-1 cells were examined and showed that selenium-enriched peptides, which are the main functional components extracted from Cardamine violifolia (CSP), increased cell viability, decreased lactate dehydrogenase activity and improved cell barrier function. Mechanistically, SEC ameliorated LPS/TNF-α-induced perturbations in mitochondrial dynamics in the jejunum and IPEC-1 cells. Moreover, CSP-mediated cell barrier function is primarily dependent on the mitochondrial fusion protein MFN2 but not MFN1. Taken together, these results indicate that SEC mitigates sepsis-induced intestinal injury, which is associated with modulating mitochondrial fusion.
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References
Andoh, A., Hirashima, M., Maeda, H., Hata, K., Inatomi, O., Tsujikawa, T., Sasaki, M., Takahashi, K., and Fujiyama, Y. (2005). Serum selenoprotein-P levels in patients with inflammatory bowel disease. Nutrition 21, 574–579.
Avery, J., and Hoffmann, P. (2018). Selenium, selenoproteins, and immunity. Nutrients 10, 1203.
Balzan, S., de Almeida Quadros, C., de Cleva, R., Zilberstein, B., and Cecconello, I. (2007). Bacterial translocation: overview of mechanisms and clinical impact. J Gastroenterol Hepatol 22, 464–471.
Bhattacharyya, A., Chattopadhyay, R., Mitra, S., and Crowe, S.E. (2014). Oxidative stress: an essential factor in the pathogenesis of gastrointestinal mucosal diseases. Physiol Rev 94, 329–354.
Chan, D.C. (2019). Mitochondrial dynamics and its involvement in disease. Annu Rev Pathol Mech Dis 15, 235–259.
Dai, Z., Li, D., Du, X., Ge, Y., Hursh, D., and Bi, X. (2020). Drosophila Caliban preserves intestinal homeostasis and lifespan through regulating mitochondrial dynamics and redox state in enterocytes. PLoS Genet 16, e1009140.
de Brito, O.M., and Scorrano, L. (2008). Mitofusin 2 tethers endoplasmic reticulum to mitochondria. Nature 456, 605–610.
de Toledo, J.H.S., Fraga-Silva, T.F.C., Borim, P.A., de Oliveira, L.R.C., Oliveira, E.S., Périco, L.L., Hiruma-Lima, C.A., de Souza, A.A.L., de Oliveira, C.A.F., Padilha, P.M., et al. (2020). Organic selenium reaches the central nervous system and downmodulates local inflammation: a complementary therapy for multiple sclerosis? Front Immunol 11, 571844.
Deng, H., Takashima, S., Paul, M., Guo, M., and Hartenstein, V. (2018). Mitochondrial dynamics regulates Drosophila intestinal stem cell differentiation. Cell Death Discov 4, 17.
Dong, A., Yu, Y., Wang, Y., Li, C., Chen, H., Bian, Y., Zhang, P., Zhao, Y., Yu, Y., and Xie, K. (2018). Protective effects of hydrogen gas against sepsis-induced acute lung injury via regulation of mitochondrial function and dynamics. Int Immunopharmacol 65, 366–372.
Guan, G., Ding, S., Yin, Y., Duraipandiyan, V., Al-Dhabi, N.A., and Liu, G. (2019). Macleaya cordata extract alleviated oxidative stress and altered innate immune response in mice challenged with enterotoxigenic Escherichia coli. Sci China Life Sci 62, 1019–1027.
Guo, Q., Li, F., Duan, Y., Wen, C., Wang, W., Zhang, L., Huang, R., and Yin, Y. (2020a). Oxidative stress, nutritional antioxidants and beyond. Sci China Life Sci 63, 866–874.
Guo, J., He, L., Li, T., Yin, J., Yin, Y., and Guan, G. (2020b). Antioxidant and anti-inflammatory effects of different zinc sources on diquat-induced oxidant stress in a piglet model. Biomed Res Int 2020, 1–10.
Handy, D.E., Joseph, J., and Loscalzo, J. (2021). Selenium, a micronutrient that modulates cardiovascular health via redox enzymology. Nutrients 13, 3238.
Haussner, F., Chakraborty, S., Halbgebauer, R., and Huber-Lang, M. (2019). Challenge to the intestinal mucosa during sepsis. Front Immunol 10, 891.
He, Y., Liu, Y., Tang, J., Jia, G., Liu, G., Tian, G., Chen, X., Cai, J., Kang, B., and Zhao, H. (2022). Selenium exerts protective effects against heat stress-induced barrier disruption and inflammation response in jejunum of growing pigs. J Sci Food Agric 102, 496–504.
Hou, J., Zhang, J., Cui, P., Zhou, Y., Liu, C., Wu, X., Ji, Y., Wang, S., Cheng, B., Ye, H., et al. (2021). TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis. J Clin Invest 131, e135197.
Kryukov, G.V., Castellano, S., Novoselov, S.V., Lobanov, A.V., Zehtab, O., Guigo, R., and Gladyshev, V.N. (2003). Characterization of mammalian selenoproteomes. Science 300, 1439–1443.
Kudva, A.K., Shay, A.E., and Prabhu, K.S. (2015). Selenium and inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 309, G71–G77.
Li, H., Che, H., Xie, J., Dong, X., Song, L., Xie, W., and Sun, J. (2022). Supplementary selenium in the form of selenylation α-D-1,6-glucan ameliorates dextran sulfate sodium induced colitis in vivo. Int J Biol Macromol 195, 67–74.
Lin, Y., Li, Y., Cong, X., Xia, Y., Huang, D., Chen, S., and Zhu, S. (2022). Selenium-enriched peptides isolated from Cardamine violifolia are potent in suppressing proliferation and enhancing apoptosis of HepG2 cells. J Food Sci 87, 3235–3247.
Liu, Y., Chen, F., Odle, J., Lin, X., Jacobi, S.K., Zhu, H., Wu, Z., and Hou, Y. (2012). Fish oil enhances intestinal integrity and inhibits TLR4 and NOD2 signaling pathways in weaned pigs after LPS challenge. J Nutr 142, 2017–2024.
Liu, J., Zhao, H., Wang, Y., Shao, Y., Zong, H., Zeng, X., and Xing, M. (2019). Arsenic trioxide and/or copper sulfate induced apoptosis and autophagy associated with oxidative stress and perturbation of mitochondrial dynamics in the thymus of Gallus gallus. Chemosphere 219, 227–235.
Luan, D., Zhao, Z., Xia, D., Zheng, Q., Gao, X., Xu, K., and Tang, B. (2021). Hydrogen selenide, a vital metabolite of sodium selenite, uncouples the sulfilimine bond and promotes the reversal of liver fibrosis. Sci China Life Sci 64, 443–451.
Ludikhuize, M.C., Meerlo, M., Gallego, M.P., Xanthakis, D., Burgaya Julià, M., Nguyen, N.T.B., Brombacher, E.C., Liv, N., Maurice, M.M., Paik, J., et al. (2020). Mitochondria define intestinal stem cell differentiation downstream of a FOXO/Notch axis. Cell Metab 32, 889–900.e7.
Lv, D., Xiong, X., Yang, H., Wang, M., He, Y., Liu, Y., and Yin, Y. (2018). Effect of dietary soy oil, glucose, and glutamine on growth performance, amino acid profile, blood profile, immunity, and antioxidant capacity in weaned piglets. Sci China Life Sci 61, 1233–1242.
Mancini, N.L., Goudie, L., Xu, W., Sabouny, R., Rajeev, S., Wang, A., Esquerre, N., Al Rajabi, A., Jayme, T.S., van Tilburg Bernandes, E., et al. (2020). Perturbed mitochondrial dynamics is a novel feature of colitis that can be targeted to lessen disease. Cell Mol Gastroenterol Hepatol 10, 287–307.
Mou, D., Ding, D., Yan, H., Qin, B., Dong, Y., Li, Z., Che, L., Fang, Z., Xu, S., Lin, Y., et al. (2020). Maternal supplementation of organic selenium during gestation improves sows and offspring antioxidant capacity and inflammatory status and promotes embryo survival. Food Funct 11, 7748–7761.
Parikh, S.M., Yang, Y., He, L., Tang, C., Zhan, M., and Dong, Z. (2015). Mitochondrial function and disturbances in the septic kidney. Semin Nephrol 35, 108–119.
Patel, R., Coulter, L.L., Rimmer, J., Parkes, M., Chinnery, P.F., and Swift, O. (2019). Mitochondrial neurogastrointestinal encephalopathy: a clinicopathological mimic of Crohn’s disease. BMC Gastroenterol 19, 11.
Plotnikov, E., Pevzner, I., Zorova, L., Chernikov, V., Prusov, A., Kireev, I., Silachev, D., Skulachev, V., and Zorov, D. (2019). Mitochondrial damage and mitochondria-targeted antioxidant protection in LPS-induced acute kidney injury. Antioxidants 8, 176.
Qasim, W., Li, Y., Sun, R.M., Feng, D.C., Wang, Z.Y., Liu, D.S., Yao, J.H., and Tian, X.F. (2020). PTEN-induced kinase 1-induced dynamin-related protein 1 Ser637 phosphorylation reduces mitochondrial fission and protects against intestinal ischemia reperfusion injury. World J Gastroenterol 26, 1758–1774.
Qu, J., Wang, W., Zhang, Q., and Li, S. (2020). Inhibition of Lipopolysaccharide-induced inflammation of chicken liver tissue by selenomethionine via TLR4-NF-κB-NLRP3 signaling pathway. Biol Trace Elem Res 195, 205–214.
Rannem, T., Ladefoged, K., Hylander, E., Hegnhøzj, J., and Jarnum, S. (1992). Selenium status in patients with Crohn’s disease. Am J Clin Nutr 56, 933–937.
Rath, E., Moschetta, A., and Haller, D. (2018). Mitochondrial function—gatekeeper of intestinal epithelial cell homeostasis. Nat Rev Gastroenterol Hepatol 15, 497–516.
Rayman, M.P. (2000). The importance of selenium to human health. Lancet 356, 233–241.
Schomburg, L. (2016). Dietary selenium and human health. Nutrients 9, 22.
Shankar-Hari, M., Phillips, G.S., Levy, M.L., Seymour, C.W., Liu, V.X., Deutschman, C.S., Angus, D.C., Rubenfeld, G.D., and Singer, M. (2016). Developing a new definition and assessing new clinical criteria for septic shock. JAMA 315, 775–787.
Sun, L.H., Pi, D.A., Zhao, L., Wang, X.Y., Zhu, L.Y., Qi, D.S., and Liu, Y. L. (2017). Response of selenium and selenogenome in immune tissues to LPS-induced inflammatory reactions in pigs. Biol Trace Elem Res 177, 90–96.
Suzuki, T. (2013). Regulation of intestinal epithelial permeability by tight junctions. Cell Mol Life Sci 70, 631–659.
Tang, W., Wu, J., Jin, S., He, L., Lin, Q., Luo, F., He, X., Feng, Y., He, B., Bing, P., et al. (2020). Glutamate and aspartate alleviate testicular/epididymal oxidative stress by supporting antioxidant enzymes and immune defense systems in boars. Sci China Life Sci 63, 116–124.
Wang, X., Liu, Y., Li, S., Pi, D., Zhu, H., Hou, Y., Shi, H., and Leng, W. (2015). Asparagine attenuates intestinal injury, improves energy status and inhibits AMP-activated protein kinase signalling pathways in weaned piglets challenged with Escherichia coli lipopolysaccharide. Br J Nutr 114, 553–565.
Wei, Y., Gao, Q., Jing, X., Zhang, Y., Zhu, H., Cong, X., Cheng, S., Liu, Y., and Xu, X. (2022). Effect of Cardamine violifolia on plasma biochemical parameters, anti-oxidative capacity, intestinal morphology, and meat quality of broilers challenged with lipopolysaccharide. Animals 12, 2497.
Xiao, K., Xu, Q., Liu, C., He, P., Qin, Q., Zhu, H., Zhang, J., Gin, A., Zhang, G., and Liu, Y. (2020). Docosahexaenoic acid alleviates cell injury and improves barrier function by suppressing necroptosis signalling in TNF-α-challenged porcine intestinal epithelial cells. Innate Immun 26, 653–665.
Xu, S., Li, L., Wu, J., An, S., Fang, H., Han, Y., Huang, Q., Chen, Z., and Zeng, Z. (2021). Melatonin attenuates sepsis-induced small-intestine injury by upregulating SIRT3-mediated oxidative-stress inhibition, mitochondrial protection, and autophagy induction. Front Immunol 12, 625627.
Yu, T., Guo, J., Zhu, S., Li, M., Zhu, Z., Cheng, S., Wang, S., Sun, Y., and Cong, X. (2020a). Protective effects of selenium-enriched peptides from Cardamine violifolia against high-fat diet induced obesity and its associated metabolic disorders in mice. RSC Adv 10, 31411–31424.
Yu, T., Guo, J., Zhu, S., Zhang, X., Zhu, Z.Z., Cheng, S., and Cong, X. (2020b). Protective effects of selenium-enriched peptides from Cardamine violifolia on D-galactose-induced brain aging by alleviating oxidative stress, neuroinflammation, and neuron apoptosis. J Funct Foods 75, 104277.
Zhang, Y., Cartland, S.P., Henriquez, R., Patel, S., Gammelgaard, B., Flouda, K., Hawkins, C.L., and Rayner, B.S. (2020). Selenomethionine supplementation reduces lesion burden, improves vessel function and modulates the inflammatory response within the setting of atherosclerosis. Redox Biol 29, 101409.
Zhang, Y., Deng, Z.X., He, M.L., Pastor, J.J., Tedo, G., Liu, J.X., and Wang, H.F. (2021). Olive oil cake extract stabilizes the physiological condition of lipopolysaccharide-challenged piglets by reducing oxidative stress and inflammatory responses and modulating the ileal microbiome. Food Funct 12, 10171–10183.
Zhao, X., Zhao, Q., Chen, H., and Xiong, H. (2019). Distribution and effects of natural selenium in soybean proteins and its protective role in soybean β-conglycinin (7S globulins) under AAPH-induced oxidative stress. Food Chem 272, 201–209.
Zheng, D., Zhou, H., Wang, H., Zhu, Y., Wu, Y., Li, Q., Li, T., and Liu, L. (2021a). Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats. Stem Cell Res Ther 12, 299.
Zheng, Y., Zhang, B., Guan, H., Jiao, X., Yang, J., Cai, J., Liu, Q., and Zhang, Z. (2021b). Selenium deficiency causes apoptosis through endoplasmic reticulum stress in swine small intestine. Biofactors 47, 788–800.
Zhu, H., Wang, H., Wang, S., Tu, Z., Zhang, L., Wang, X., Hou, Y., Wang, C., Chen, J., and Liu, Y. (2018). Flaxseed oil attenuates intestinal damage and inflammation by regulating necroptosis and TLR4/NOD signaling pathways following lipopolysaccharide challenge in a piglet model. Mol Nutr Food Res 62, 1700814.
Zhu, S., Du, C., Yu, T., Cong, X., Liu, Y., Chen, S., and Li, Y. (2019). Antioxidant activity of selenium-enriched peptides from the protein hydrolysate of Cardamine violifolia. J Food Sci 84, 3504–3511.
Zhu, S., Yang, W., Lin, Y., Du, C., Huang, D., Chen, S., Yu, T., and Cong, X. (2021). Antioxidant and anti-fatigue activities of selenium-enriched peptides isolated from Cardamine violifolia protein hydrolysate. J Funct Foods 79, 104412.
Zhu, X., Sun, M., Guo, H., Lu, G., Gu, J., Zhang, L., Shi, L., Gao, J., Zhang, D., Wang, W., et al. (2022). Verbascoside protects from LPS-induced septic cardiomyopathy via alleviating cardiac inflammation, oxidative stress and regulating mitochondrial dynamics. Ecotoxicol Environ Saf 233, 113327.
Zuo, L., Kuo, W.T., and Turner, J.R. (2020). Tight junctions as targets and effectors of mucosal immune homeostasis. Cell Mol Gastroenterol Hepatol 10, 327–340.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (U22A20517, 32272906 and 32102566), and the Project of Wuhan Science and Technology Bureau (2022020801010391).
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Selenium-enriched Cardamine violifolia protects against sepsis-induced intestinal injury by regulating mitochondrial fusion in weaned pigs
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Wang, D., Kuang, Y., Lv, Q. et al. Selenium-enriched Cardamine violifolia protects against sepsis-induced intestinal injury by regulating mitochondrial fusion in weaned pigs. Sci. China Life Sci. 66, 2099–2111 (2023). https://doi.org/10.1007/s11427-022-2274-7
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DOI: https://doi.org/10.1007/s11427-022-2274-7