SUCCINATE CONFERS STRONGER CYTOPROTECTION IN KIDNEY CELLS THAN IN ASTROCYTES DUE TO ITS MORE EFFICIENT INVOLVEMENT IN ENERGY METABOLISM

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Being among the most metabolically active organs, brain and kidneys critically depend on efficient energy metabolism, which primarily relies on oxidative phosphorylation. Acute pathological conditions associated with a lack of metabolic substrates or their impaired utilization trigger signaling cascades that initiate cell death and lead to poorly reversible organ dysfunction. One of the therapeutic approaches to correct the energy deficit is administration of exogenous metabolites of the tricarboxylic acid cycle, such as succinate. In this study, we investigated the effects of exogenous succinate on astrocytes and renal epithelial cells under normal conditions and in serum deprivation-induced injury. Incubation with succinate increased the viability of both cell types under normal and pathological conditions, but a more pronounced cytoprotective effect was observed in renal cells. In injured renal epithelial cells, succinate increased mitochondrial membrane potential, a critical parameter for the maintenance of mitochondrial function and ATP generation. Comparison of respiration and oxidative phosphorylation parameters in astrocytes and renal epithelial cells in the presence of exogenous succinate revealed that epithelial cells exhibited a significantly higher respiratory control and lower proton leak compared to astrocytes, which correlated with the higher cytoprotective activity of succinate for kidney cells. Therefore, succinate showed a noticeable positive effect in the renal epithelium both under normal conditions and after serum deprivation; however, in astrocytes, its effect was less pronounced. This discrepancy might be related to a more efficient succinate utilization by the mitochondria in renal cells and intrinsic bioenergetic differences between astrocytes and epithelial cells. Despite the clinical use of succinate-containing drugs, the determination of optimal dosages and development of effective therapeutic regimens require further investigation. Our results demonstrate cell type-dependent differences in the efficacy of succinate, suggesting that its therapeutic potential may differ significantly depending on the organ-specific bioenergetic and metabolic properties.

About the authors

M. I. Buyan

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University

Moscow, Russia; Moscow, Russia

K. S. Cherkesova

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University; Faculty of Biology, Lomonosov Moscow State University

Moscow, Russia; Moscow, Russia

A. A. Brezgunova

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Moscow, Russia

I. B. Pevzner

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Moscow, Russia

N. V. Andrianova

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Moscow, Russia

E. Yu. Plotnikov

A. N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University

Email: plotnikov@belozersky.msu.ru
Moscow, Russia

References

  1. Duann, P., and Lin, P.-H. (2017) Mitochondria damage and kidney disease, Adv. Exp. Med. Biol., 982, 529-551, https://doi.org/10.1007/978-3-319-55330-6_27.
  2. Gong, M., Li, Z., Zhang, X., Liu, B., Luo, J., Qin, X., and Wei, Y. (2021) PTEN mediates serum deprivation-induced cytotoxicity in H9c2 cells via the PI3K/AKT signaling pathway, Toxicol. In Vitro, 73, 105131, https://doi.org/10.1016/j.tiv.2021.105131.
  3. Forbes, J. M. (2016) Mitochondria-power players in kidney function? Trends Endocrinol. Metab., 27, 441-442, https://doi.org/10.1016/j.tem.2016.05.002.
  4. Hoenig, M. P., and Zeidel, M. L. (2014) Homeostasis, the milieu intérieur, and the wisdom of the nephron, Clin. J. Am. Soc. Nephrol., 9, 1272-1281, https://doi.org/10.2215/CJN.08860813.
  5. Wang, Z., Ying, Z., Bosy-Westphal, A., Zhang, J., Schautz, B., Later, W., Heymsfield, S. B., and Müller, M. J. (2010) Specific metabolic rates of major organs and tissues across adulthood: evaluation by mechanistic model of resting energy expenditure, Am. J. Clin. Nutr., 92, 1369-1377, https://doi.org/10.3945/ajcn.2010.29885.
  6. Ho, H.-J., and Shirakawa, H. (2022) Oxidative stress and mitochondrial dysfunction in chronic kidney disease, Cells, 12, 88, https://doi.org/10.3390/cells12010088.
  7. Cunnane, S. C., Trushina, E., Morland, C., Prigione, A., Casadesus, G., Andrews, Z. B., Beal, M. F., Bergersen, L. H., Brinton, R. D., de la Monte, S., Eckert, A., Harvey, J., Jeggo, R., Jhamandas, J. H., Kann, O., la Cour, C. M., Martin, W. F., Mithieux, G., Moreira, P. I., et al. (2020) Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing, Nat. Rev. Drug Discov., 19, 609-633, https://doi.org/10.1038/s41573-020-0072-x.
  8. Song, N., Mei, S., Wang, X., Hu, G., and Lu, M. (2024) Focusing on mitochondria in the brain: from biology to therapeutics, Transl. Neurodegener., 13, 23, https://doi.org/10.1186/s40035-024-00409-w.
  9. Pellerin, L., and Magistretti, P. J. (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization, Proc. Natl. Acad. Sci. USA, 91, 10625-10629, https://doi.org/10.1073/pnas.91.22.10625.
  10. Kasischke, K. A., Vishwasrao, H. D., Fisher, P. J., Zipfel, W. R., and Webb, W. W. (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis, Science, 305, 99-103, https://doi.org/10.1126/science.1096485.
  11. Qiu, T., He, Y.-Y., Zhang, X., and Ma, X.-L. (2018) Novel role of ER stress and mitochondria stress in serum-deprivation induced apoptosis of rat mesenchymal stem cells, Curr. Med. Sci., 38, 229-235, https://doi.org/10.1007/s11596-018-1870-9.
  12. Andrianova, N. V., Buyan, M. I., Brezgunova, A. A., Cherkesova, K. S., Zorov, D. B., and Plotnikov, E. Y. (2025) Hemorrhagic shock and mitochondria: pathophysiology and therapeutic approaches, Int. J. Mol. Sci., 26, 1843, https://doi.org/10.3390/ijms26051843.
  13. Nguyen, H., Zerimech, S., and Baltan, S. (2021) Astrocyte mitochondria in white-matter injury, Neurochem. Res., 46, 2696-2714, https://doi.org/10.1007/s11064-021-03239-8.
  14. Belenguer, P., Duarte, J. M. N., Schuck, P. F., and Ferreira, G. C. (2019) Mitochondria and the brain: bioenergetics and beyond, Neurotox. Res., 36, 219-238, https://doi.org/10.1007/s12640-019-00061-7.
  15. Bonvento, G., and Bolaños, J. P. (2021) Astrocyte-neuron metabolic cooperation shapes brain activity, Cell Metab., 33, 1546-1564, https://doi.org/10.1016/j.cmet.2021.07.006.
  16. Zhang, L.-Y., Hu, Y.-Y., Liu, X.-Y., Wang, X.-Y., Li, S.-C., Zhang, J.-G., Xian, X.-H., Li, W.-B., and Zhang, M. (2024) The role of astrocytic mitochondria in the pathogenesis of brain ischemia, Mol. Neurobiol., 61, 2270-2282, https://doi.org/10.1007/s12035-023-03714-z.
  17. Bhargava, P., and Schnellmann, R. G. (2017) Mitochondrial energetics in the kidney, Nat. Rev. Nephrol., 13, 629-646, https://doi.org/10.1038/nrneph.2017.107.
  18. Ma, H., Guo, X., Cui, S., Wu, Y., Zhang, Y., Shen, X., Xie, C., and Li, J. (2022) Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction, Kidney Int., 101, 315-330, https://doi.org/10.1016/j.kint.2021.10.028.
  19. Huang, R., Zhang, C., Xiang, Z., Lin, T., Ling, J., and Hu, H. (2024) Role of mitochondria in renal ischemia-reperfusion injury, FEBS J., 291, 5365-5378, https://doi.org/10.1111/febs.17130.
  20. Liu, F., Lu, J., Manaenko, A., Tang, J., and Hu, Q. (2018) Mitochondria in ischemic stroke: new insight and implications, Aging Dis., 9, 924-937, https://doi.org/10.14336/AD.2017.1126.
  21. Jurcau, A., and Ardelean, A. I. (2022) Oxidative stress in ischemia/reperfusion injuries following acute ischemic stroke, Biomedicines, 10, 574, https://doi.org/10.3390/biomedicines10030574.
  22. Zhang, X., Agborbesong, E., and Li, X. (2021) The role of mitochondria in acute kidney injury and chronic kidney disease and its therapeutic potential, Int. J. Mol. Sci., 22, 11253, https://doi.org/10.3390/ijms222011253.
  23. Lan, R., Geng, H., Singha, P. K., Saikumar, P., Bottinger, E. P., Weinberg, J. M., and Venkatachalam, M. A. (2016) Mitochondrial pathology and glycolytic shift during proximal tubule atrophy after ischemic AKI, J. Am. Soc. Nephrol., 27, 3356-3367, https://doi.org/10.1681/ASN.2015020177.
  24. Lorenz, M., Fritsche-Guenther, R., Bartsch, C., Vietzke, A., Eisenberger, A., Stangl, K., Stangl, V., and Kirwan, J. A. (2023) Serum starvation accelerates intracellular metabolism in endothelial cells, Int. J. Mol. Sci., 24, 1189, https://doi.org/10.3390/ijms24021189.
  25. Chouchani, E. T., Pell, V. R., Gaude, E., Aksentijević, D., Sundier, S. Y., Robb, E. L., Logan, A., Nadtochiy, S. M., Ord, E. N. J., Smith, A. C., Eyassu, F., Shirley, R., Hu, C.-H., Dare, A. J., James, A. M., Rogatti, S., Hartley, R. C., Eaton, S., Costa, A. S. H., et al. (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS, Nature, 515, 431-435, https://doi.org/10.1038/nature13909.
  26. Pajor, A. M. (2014) Sodium-coupled dicarboxylate and citrate transporters from the SLC13 family, Pflugers Arch., 466, 119-130, https://doi.org/10.1007/s00424-013-1369-y.
  27. Pajor, A. M. (2000) Molecular properties of sodium/dicarboxylate cotransporters, J. Membr. Biol., 175, 1-8, https://doi.org/10.1007/s002320001049.
  28. Yodoya, E., Wada, M., Shimada, A., Katsukawa, H., Okada, N., Yamamoto, A., Ganapathy, V., and Fujita, T. (2006) Functional and molecular identification of sodium-coupled dicarboxylate transporters in rat primary cultured cerebrocortical astrocytes and neurons, J. Neurochem., 97, 162-173, https://doi.org/10.1111/j.1471-4159.2006.03720.x.
  29. Giorgi-Coll, S., Amaral, A. I., Hutchinson, P. J. A., Kotter, M. R., and Carpenter, K. L. H. (2017) Succinate supplementation improves metabolic performance of mixed glial cell cultures with mitochondrial dysfunction, Sci. Rep., 7, 1003, https://doi.org/10.1038/s41598-017-01149-w.
  30. Wang, Y., Huang, C., Wang, X., Cheng, R., Li, X., Wang, J., Zhang, L., Li, F., Wang, H., Li, X., Li, Y., Xia, Y., Cheng, J., Pan, X., Jia, J., and Xiao, G.-D. (2025) Succinate activates uncoupling protein 2 to suppress neuroinflammation and confer protection following intracerebral hemorrhage, Antioxid. Redox Signal., 42, 687-710, https://doi.org/10.1089/ars.2024.0573.
  31. Jalloh, I., Helmy, A., Howe, D. J., Shannon, R. J., Grice, P., Mason, A., Gallagher, C. N., Stovell, M. G., van der Heide, S., Murphy, M. P., Pickard, J. D., Menon, D. K., Carpenter, T. A., Hutchinson, P. J., and Carpenter, K. L. (2017) Focally perfused succinate potentiates brain metabolism in head injury patients, J. Cereb. Blood Flow Metab., 37, 2626-2638, https://doi.org/10.1177/0271678X16672665.
  32. Khellaf, A., Garcia, N. M., Tajsic, T., Alam, A., Stovell, M. G., Killen, M. J., Howe, D. J., Guilfoyle, M. R., Jalloh, I., Timofeev, I., Murphy, M. P., Carpenter, T. A., Menon, D. K., Ercole, A., Hutchinson, P. J., Carpenter, K. L., Thelin, E. P., and Helmy, A. (2022) Focally administered succinate improves cerebral metabolism in traumatic brain injury patients with mitochondrial dysfunction, J. Cereb. Blood Flow Metab., 42, 39-55, https://doi.org/10.1177/0271678X211042112.
  33. Stovell, M. G., Mada, M. O., Helmy, A., Carpenter, T. A., Thelin, E. P., Yan, J.-L., Guilfoyle, M. R., Jalloh, I., Howe, D. J., Grice, P., Mason, A., Giorgi-Coll, S., Gallagher, C. N., Murphy, M. P., Menon, D. K., Hutchinson, P. J., and Carpenter, K. L. H. (2018) The effect of succinate on brain NADH/NAD+ redox state and high energy phosphate metabolism in acute traumatic brain injury, Sci. Rep., 8, 11140, https://doi.org/10.1038/s41598-018-29255-3.
  34. Malakhova, V. I., Godukhin, O. V., and Kondrashova, M. N. (1992) Influence of succinate on the effectiveness of glutamatergic synaptic transmission in surviving slices of rat hippocampus [in Russian], Neurofiziologiia, 24, 238-243.
  35. Nowak, G., Clifton, G. L., and Bakajsova, D. (2008) Succinate ameliorates energy deficits and prevents dysfunction of complex I in injured renal proximal tubular cells, J. Pharmacol. Exp. Ther., 324, 1155-1162, https://doi.org/10.1124/jpet.107.130872.
  36. Panov, A., Mayorov, V. I., and Dikalov, S. (2022) Metabolic syndrome and β-oxidation of long-chain fatty acids in the brain, heart, and kidney mitochondria, Int. J. Mol. Sci., 23, 4047, https://doi.org/10.3390/ijms23074047.
  37. Pu, M., Zhang, J., Hong, F., Wang, Y., Zhang, C., Zeng, Y., Fang, Z., Qi, W., Yang, X., Gao, G., and Zhou, T. (2024) The pathogenic role of succinate-SUCNR1: a critical function that induces renal fibrosis via M2 macrophage, Cell Commun. Signal., 22, 78, https://doi.org/10.1186/s12964-024-01481-5.
  38. Moyon, A., Garrigue, P., Balasse, L., Fernandez, S., Brige, P., Bouhlel, A., Hache, G., Dignat-George, F., Taïeb, D., and Guillet, B. (2021) Succinate injection rescues vasculature and improves functional recovery following acute peripheral ischemia in rodents: a multimodal imaging study, Cells, 10, 795, https://doi.org/10.3390/cells10040795.
  39. Sapieha, P., Sirinyan, M., Hamel, D., Zaniolo, K., Joyal, J.-S., Cho, J.-H., Honoré, J.-C., Kermorvant-Duchemin, E., Varma, D. R., Tremblay, S., Leduc, M., Rihakova, L., Hardy, P., Klein, W. H., Mu, X., Mamer, O., Lachapelle, P., di Polo, A., Beauséjour, C., et al. (2008) The succinate receptor GPR91 in neurons has a major role in retinal angiogenesis, Nat. Med., 14, 1067-1076, https://doi.org/10.1038/nm.1873.
  40. Wu, K. K. (2023) Extracellular succinate: a physiological messenger and a pathological trigger, Int. J. Mol. Sci., 24, 11165, https://doi.org/10.3390/ijms241311165.
  41. Huang, H., Li, G., He, Y., Chen, J., Yan, J., Zhang, Q., Li, L., and Cai, X. (2024) Cellular succinate metabolism and signaling in inflammation: implications for therapeutic intervention, Front. Immunol., 15, 1404441, https://doi.org/10.3389/fimmu.2024.1404441.
  42. Zhang, W., and Lang, R. (2023) Succinate metabolism: a promising therapeutic target for inflammation, ischemia/reperfusion injury and cancer, Front. Cell Dev. Biol., 11, 1266973, https://doi.org/10.3389/fcell.2023.1266973.
  43. Koyasu, S., Kobayashi, M., Goto, Y., Hiraoka, M., and Harada, H. (2018) Regulatory mechanisms of hypoxia-inducible factor 1 activity: two decades of knowledge, Cancer Sci., 109, 560-571, https://doi.org/10.1111/cas.13483.
  44. Semenza, G. L. (2010) Hypoxia-inducible factor 1: regulator of mitochondrial metabolism and mediator of ischemic preconditioning, Biochim. Biophys. Acta, 1813, 1263-1268, https://doi.org/10.1016/j.bbamcr.2010.08.006.
  45. Fukuda, R., Zhang, H., Kim, J. W., Shimoda, L., Dang, C. V., and Semenza, G. L. (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells, Cell, 129, 111-122, https://doi.org/10.1016/j.cell.2007.01.047.
  46. Piel, S., Ehinger, J. K., Chamkha, I., Frostner, E. Å., Sjövall, F., Elmér, E., and Hansson, M. J. (2018) Bioenergetic bypass using cell-permeable succinate, but not methylene blue, attenuates metformin-induced lactate production, Intensive Care Med. Exp., 6, 22, https://doi.org/10.1186/s40635-018-0186-1.
  47. Owiredu, S., Ranganathan, A., Eckmann, D. M., Shofer, F. S., Hardy, K., Lambert, D. S., Kelly, M., and Jang, D. H. (2020) Ex vivo use of cell-permeable succinate prodrug attenuates mitochondrial dysfunction in blood cells obtained from carbon monoxide-poisoned individuals, Am. J. Physiol. Cell Physiol., 319, C129-C135, https://doi.org/10.1152/ajpcell.00539.2019.
  48. Owiredu, S., Ranganathan, A., Greenwood, J. C., Piel, S., Janowska, J. I., Eckmann, D. M., Kelly, M., Ehinger, J. K., Kilbaugh, T. J., and Jang, D. H. (2020) In vitro comparison of hydroxocobalamin (B12a) and the mitochondrial directed therapy by a succinate prodrug in a cellular model of cyanide poisoning, Toxicol. Rep., 7, 1263-1271, https://doi.org/10.1016/j.toxrep.2020.09.002.
  49. Bețiu, A. M., Chamkha, I., Gustafsson, E., Meijer, E., Avram, V. F., Åsander Frostner, E., Ehinger, J. K., Petrescu, L., Muntean, D. M., and Elmér, E. (2021) Cell-permeable succinate rescues mitochondrial respiration in cellular models of amiodarone toxicity, Int. J. Mol. Sci., 22, 11786, https://doi.org/10.3390/ijms222111786.
  50. Janowska, J. I., Piel, S., Saliba, N., Kim, C. D., Jang, D. H., Karlsson, M., Kilbaugh, T. J., and Ehinger, J. K. (2020) Mitochondrial respiratory chain complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug, Toxicol In Vitro, 65, 104794, https://doi.org/10.1016/j.tiv.2020.104794.
  51. Avram, V. F., Bîna, A. M., Sima, A., Aburel, O. M., Sturza, A., Burlacu, O., Timar, R. Z., Muntean, D. M., Elmér, E., and Crețu, O. M. (2021) Improvement of platelet respiration by cell-permeable succinate in diabetic patients treated with statins, Life (Basel), 11, 288, https://doi.org/10.3390/life11040288.
  52. Avram, V. F., Chamkha, I., Åsander-Frostner, E., Ehinger, J. K., Timar, R. Z., Hansson, M. J., Muntean, D. M., and Elmér, E. (2021) Cell-permeable succinate rescues mitochondrial respiration in cellular models of statin toxicity, Int. J. Mol. Sci., 22, 424, https://doi.org/10.3390/ijms22010424.
  53. Vinokurov, A. Y., Popov, S. V., Belyakov, D. Y., Popov, D. Y., Nikulin, A. S., Zakrzhevskaya, V. D., Guseinov, R. G., Sivak, K. V., Dunaev, A. V., Potapova, E. V., and Abramov, A. Yu. (2025) Cytoprotective action of sodium fumarate in an in vitro model of hypoxia using sodium dithionite, Sovrem. Tekhnologii Med., 17, 93-106, https://doi.org/10.17691/stm2025.17.1.09.
  54. Takasu, C., Vaziri, N. D., Li, S., Robles, L., Vo, K., Takasu, M., Pham, C., Liu, S., Farzaneh, S. H., Foster, C. E., Stamos, M. J., and Ichii, H. (2015) Treatment with dimethyl fumarate attenuates calcineurin inhibitor-induced nephrotoxicity, Transplantation, 99, 1144-1150, https://doi.org/10.1097/TP.0000000000000647.
  55. Zhou, K., Xie, M., Yi, S., Tang, Y., Luo, H., Xiao, Q., Xiao, J., and Li, Y. (2021) Dimethyl fumarate ameliorates endotoxin-induced acute kidney injury against macrophage oxidative stress, Ren. Fail., 43, 1229-1239, https://doi.org/10.1080/0886022X.2021.1963774.
  56. An, X., Yin, M., Shen, Y., Guo, X., Xu, Y., Cheng, D., and Gui, D. (2025) Dimethyl fumarate ameliorated pyroptosis in contrast-induced acute renal injury by regulating endoplasmic reticulum stress and JAK2-STAT3 pathway, Ren. Fail., 47, 2504633, https://doi.org/10.1080/0886022X.2025.2504633.
  57. Ashari, S., Naghsh, N., Salari, Y., Barghi, N. G., and Bagheri, A. (2023) Dimethyl fumarate attenuates Di-­(2-ethylhexyl) phthalate-induced nephrotoxicity through the Nrf2/HO-1 and NF-κB signaling pathways, Inflammation, 46, 453-467, https://doi.org/10.1007/s10753-022-01746-6.
  58. Yang, Y., Cai, F., Zhou, N., Liu, S., Wang, P., Zhang, S., Zhang, Y., Zhang, A., Jia, Z., and Huang, S. (2021) Dimethyl fumarate prevents ferroptosis to attenuate acute kidney injury by acting on NRF2, Clin. Transl. Med., 11, e382, https://doi.org/10.1002/ctm2.382.
  59. Zhao, X., Sun, G., Zhang, J., Ting, S.-M., Gonzales, N., and Aronowski, J. (2015) Dimethyl fumarate protects brain from damage produced by intracerebral hemorrhage by mechanism involving Nrf2, Stroke, 46, 1923-1928, https://doi.org/10.1161/STROKEAHA.115.009398.
  60. Iniaghe, L. O., Krafft, P. R., Klebe, D. W., Omogbai, E. K. I., Zhang, J. H., and Tang, J. (2015) Dimethyl fumarate confers neuroprotection by casein kinase 2 phosphorylation of Nrf2 in murine intracerebral hemorrhage, Neurobiol. Dis., 82, 349-358, https://doi.org/10.1016/j.nbd.2015.07.001.
  61. Casili, G., Campolo, M., Paterniti, I., Lanza, M., Filippone, A., Cuzzocrea, S., and Esposito, E. (2018) Dimethyl fumarate attenuates neuroinflammation and neurobehavioral deficits induced by experimental traumatic brain injury, J. Neurotrauma, 35, 1437-1451, https://doi.org/10.1089/neu.2017.5260.
  62. Krämer, T., Grob, T., Menzel, L., Hirnet, T., Griemert, E., Radyushkin, K., Thal, S. C., Methner, A., and Schaefer, M. K. E. (2017) Dimethyl fumarate treatment after traumatic brain injury prevents depletion of antioxidative brain glutathione and confers neuroprotection, J. Neurochem., 143, 523-533, https://doi.org/10.1111/jnc.14220.
  63. Yao, Y., Miao, W., Liu, Z., Han, W., Shi, K., Shen, Y., Li, H., Liu, Q., Fu, Y., Huang, D., and Shi, F.-D. (2016) Dimethyl fumarate and monomethyl fumarate promote post-ischemic recovery in mice, Transl. Stroke Res., 7, 535-547, https://doi.org/10.1007/s12975-016-0496-0.
  64. Singh, D., Reeta, K. H., Sharma, U., Jagannathan, N. R., Dinda, A. K., and Gupta, Y. K. (2019) Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region, Neurochem. Int., 126, 96-108, https://doi.org/10.1016/j.neuint.2019.03.010.
  65. Clausen, B. H., Lundberg, L., Yli-Karjanmaa, M., Martin, N. A., Svensson, M., Alfsen, M. Z., Flæng, S. B., Lyngsø, K., Boza-Serrano, A., Nielsen, H. H., Hansen, P. B., Finsen, B., Deierborg, T., Illes, Z., and Lambertsen, K. L. (2017) Fumarate decreases edema volume and improves functional outcome after experimental stroke, Exp. Neurol., 295, 144-154, https://doi.org/10.1016/j.expneurol.2017.06.011.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025 Russian Academy of Sciences

Согласие на обработку персональных данных

 

Используя сайт https://journals.rcsi.science, я (далее – «Пользователь» или «Субъект персональных данных») даю согласие на обработку персональных данных на этом сайте (текст Согласия) и на обработку персональных данных с помощью сервиса «Яндекс.Метрика» (текст Согласия).