EVALUATION OF THE PROTECTIVE EFFECT OF MITOCHONDRIAL OXIDATION SUBSTRATES ON THE ENERGY METABOLISM OF THE SMALL INTESTINE IN THE EARLY STAGES AFTER EXTERNAL IRRADIATION
Abstract
Background. The tissue of the small intestine is sensitive to radiation exposure. The key element of the damage is energy metabolism disturbance. Tissue respiration substrates can regulate and protect the mitochondrial oxidation system. Their effect on the energy metabolism of the small intestine in the early stages after irradiation has not been sufficiently studied. Objective. To evaluate the effect of mitochondrial oxidation substrates on the energy metabolism of small intestinal tissue fragments of laboratory rats on the 3rd and 10th days after a single external irradiation at a dose of 0.5 and 1 Gy. Material and methods. Two groups of white male Wistar rats (weight 150-220 g) were irradiated using IGUR-1 facility (source 137Cs) at a dose of 0.5 and 1 Gy (power 0.92 Gy/min). A mixture of succinate and potassium glutamate in gelatin capsules (25 mg/ kg of body weight) was added to the diet of the irradiated animals over the period of 3-10 days. On the 3rd and 10th days, the parameters of mitochondrial oxidation of small intestinal tissue fragments were evaluated using the polarographic method. Results. The introduction of succinate and potassium glutamate over the period of 3 days had a positive effect on energy parameters: the rate of endogenous respiration corresponded to that of the comparison group, the intensity of oxygen consumption on exogenous substrates improved as well. On day 10, the combination of substrates stimulated both endogenous and substrate respiration (p <0.05). The effect was more pronounced in groups with a dose of 1 Gy. Conclusion. The introduction of succinate and glutamate into the diet of irradiated laboratory rats restores energy metabolism in small intestinal tissues due to the replenishment of substrates, thus ensuring a protective effect and preservation of mitochondria.
References
Asano J, Sato T, Ichinose S, Kajita M, Onai N, Shimizu S, Ohteki T. Intrinsic Autophagy Is Required for the Maintenance of Intestinal Stem Cells and for Irradiation-Induced Intestinal Regeneration. Cell Rep. 2017;20(5):1050-1060. https://doi.org/10.1016/j.celrep.2017.07.019.
Berliner C. Are the solutions to radiotherapy side effects on the gastrointestinal tract right at our doorstep? EBioMedicine. 2021;74:103687. https://doi.org/10.1016/j.ebiom.2021.103687.
Wu W, Cai Y, Yang Z, Chen M, Hu J, Qu K, Yang J. Radiation-induced intestinal injury: from molecular mechanisms to clinical translation. Oncol Rev. 2025;19:1613704. https://doi.org/10.3389/or.2025.1613704.
Hu Z, Zhang J, Li H, Wang X, Zhang G, Cui H, Nian J. Research progress on the hallmarks of radiation-induced intestinal injury: Mechanisms, biomarkers and therapeutic targets. Arch Biochem Biophys. 2025;772:110562. https://doi.org/10.1016/j.abb.2025.110562.
Zhang SB, Maguire D, Zhang M, Tian Y, Yang S, Zhang A, Casey-Sawicki K, Han D, Ma J, Yin L, Guo Y, Wang X, Chen C, Litvinchuk A, Zhang Z, Swarts S, Vidyasagar S, Zhang L, Okunieff P. Mitochondrial DNA and functional investigations into the radiosensitivity of four mouse strains. Int J Cell Biol. 2014;2014:850460. https://doi.org/10.1155/2014/850460.
Farhood B, Ashrafizadeh M, Khodamoradi E, Hoseini-Ghahfarokhi M, Afrashi S, Musa AE, Najafi M. Targeting of cellular redox metabolism for mitigation of radiation injury. Life Sci. 2020;250:117570. https://doi.org/10.1016/j.lfs.2020.117570.
Ho GT, Theiss AL. Mitochondria and Inflammatory Bowel Diseases: Toward a Stratified Therapeutic Intervention. Annu Rev Physiol. 2022;84:435-459. https://doi.org/10.1146/annurev-physiol-060821-083306.
Khodamoradi E, Hoseini-Ghahfarokhi M, Amini P, Motevaseli E, Shabeeb D, Musa AE, Najafi M, Farhood B. Targets for protection and mitigation of radiation injury. Cell Mol Life Sci. 2020;77(16):3129-3159. https://doi.org/10.1007/s00018-020-03479-x.
Huang Y, Lv X, Si T, Meng X, Liao X, Zhang P, Peng Z, Zhou Z, Yi P, Huang S. Immuno-protective impact and clinical translation of radioprotective agents in cancer radiotherapy. Front Immunol. 2025;16:1610296. https://doi.org/10.3389/fimmu.2025.1610296.
Litvinchuk AV, Logvinovich OS, Shpankov АО, Dokhov OV, Myshkavets NS, Belous EM. Himicheskie i prirodnye substancii dlja zashhity ot radiacionnogo porazhenija [Chemical and natural substances for protection against radiation]. Problemy zdorovja i jekologii [Health and Ecology Issues]. 2024;21(4):16-25. https://doi.org/10.51523/2708-6011.2024-21-4-02. (Russian).
Connors J, Dawe N, Van Limbergen J. The Role of Succinate in the Regulation of Intestinal Inflammation. Nutrients. 2018;11(1):25. https://doi.org/10.3390/nu11010025.
Wei YH, Ma X, Zhao JC, Wang XQ, Gao CQ. Succinate metabolism and its regulation of host-microbe interactions. Gut Microbes. 2023;15(1):2190300. https://doi.org/10.1080/19490976.2023.2190300.
Ashastin BV. Vozmozhnosti podderzhanija mitohondrial"nogo apparata pri gipoksii substratami jenergeticheskogo obmena [Possibilities of maintenance of the mitochondrial device at the hypoxemia substrata of the power exchange]. Vestnik Juzhno-Uralskogo gosudarstvennogo universiteta. Serija: Obrazovanie, zdravoohranenie, fizicheskaja kultura. 2012;42:114-118. (Russian).
Rong J, Yu Q, Huang G, Wang Y, Zhang N. Advances in mitochondrial dysfunction in radiation tissue injury. Front Physiol. 2025;16:1660330. https://doi.org/10.3389/fphys.2025.1660330.
Averbeck D. Low-Dose Non-Targeted Effects and Mitochondrial Control. Int J Mol Sci. 2023;24(14):11460. https://doi.org/10.3390/ijms241411460.
Myshkavets NS, Babenka AS, Alekseiko LN, Kuzniatsou OE. Sostojanie jenergeticheskogo obmena tkani tonkogo kishechnika laboratornyh krys posle vozdejstvija odnokratnogo vneshnego Γamma-obluchenija [Energetic metabolism state of small intestine tissue in laboratory rats after single external γ-radiation exposure]. Biohimija i molekuljarnaja biologija [Biochemistry and molecular biology]. 2025;2(7):33-41. (Russian).
Myshkavets NS. Izmenenie urovnja jendogennogo dyhanija slizistoj tonkogo kishechnika v razlichnye sroki posle obluchenija [Changes in the level of endogenous respiration of the small intestine mucosa at various times after irradiation]. Problemy zdorovja i jekologii [Health and Ecology Issues]. 2023;20(2):72-77. https://doi.org/10.51523/2708-6011.2023-20-2-10. (Russian).
Frank GM, Kondrashova MN, Mohova EN, Rotenberg JuS, editors. Rukovodstvo po izucheniju biologicheskogo okislenija poljarograficheskim metodom. Moskva: Nauka; 1973. 221 p. (Russian).
Barkovskij EV, Bokut SB, Borodinskij AN, Buko VI. Sovremennye problemy biohimii: metody issledovanij. Minsk: Vyshjejshaja shkola; 2013. 491 p. (Russian).
Orlov YuP, Butrov AV, Sviridov SV, Afanasiev VV, Kondratiev AN, Tsentsiper LM, Govorova NV, Kondratiev AI, Baytugaeva GA, Kakulya EN. Sukcinat i sukcinatdegidrogenaza kak "tochka opory" v cikle Krebsa pri kriticheskih sostojanijah [Succinate and succinate dehydrogenase as a "foothold" in the Krebs cycle in critical conditions]. Antibiotiki i Himioterapija [Antibiotics and Chemotherapy]. 2023;68(1-2):57-68. https://doi.org/10.37489/0235-29902023-68-1-2-57-68. (Russian).
Cao Z, Mu S, Wang M, Zhang Y, Zou G, Yuan X, Huang Y, Yu S, Zhang J, Zhang C. Succinate pretreatment attenuates intestinal ischemia-reperfusion injury by inhibiting necroptosis and inflammation via upregulating Klf4. Int Immunopharmacol. 2023;120:110425. https://doi.org/10.1016/j.intimp.2023.110425.
Zhou Z, Yu L, Cao J, Yu J, Lin Z, Hong Y, Jiang S, Chen C, Mi Y, Zhang C, Li J. Lactobacillus salivarius Promotion of Intestinal Stem Cell Activity in Hens Is Associated with Succinate-Induced Mitochondrial Energy Metabolism. mSystems. 2022;7(6):e0090322. https://doi.org/10.1128/msystems.00903-22.
Morris O, Jasper H. Reactive Oxygen Species in intestinal stem cell metabolism, fate and function. Free Radic Biol Med. 2021;166:140-146. https://doi.org/10.1016/j.freeradbiomed.2021.02.015.
Nath A, Chakrabarti P, Sen S, Barui A. Reactive Oxygen Species in Modulating Intestinal Stem Cell Dynamics and Function. Stem Cell Rev Rep. 2022;18(7):2328-2350. https://doi.org/10.1007/s12015-022-10377-1.
Zhao M, Zhou C, Wang D, Wu Q, Feng B. Succinate's Dual Roles in Inflammatory Bowel Disease: A Narrative Review of Microbiota-Metabolism-Immune Crosstalk and Therapeutic Implications. J Inflamm Res. 2025;18:15017-15032. https://doi.org/10.2147/JIR.S561871.
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