ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2021, 6(6): 289–299
https://doi.org/10.26693/jmbs06.06.289
Biology

The State of the Neuronal-Astrocytic Apparatus of the Hippocampus on the Background of Long-Term Administration of Isoniazid and Rifampicin under Conditions of Correction of the Gut Microflora

Kharchenko Yu. V. 1, Myakushko V. A. 2, Trushenko O. S. 2, Yevtushenko T. V. 2, Yevtushenko N. V. 2, Derkach A. K. 2, Kravchenko M. K. 2
Abstract

The purpose of the study was to determine the morphometric and ultrastructural features of neurons and glial cells, as well as the levels of glial fibrillar acid protein in the hippocampus of rats under long-term administration of isoniazid and rifampicin during experimental therapy with a combination of pro/prebiotics. Materials and methods. The studies were conducted on three groups of white Wistar male rats with drug-induced hepatitis, reproduced by intragastric administration of isoniazid and rifampicin for 28 days. In the last 14 days of the intragastric experiment, rats of the research group were administered probiotic and prebiotic. The content of cytosolic glial fibrillar acid protein in the hippocampus was determined by competitive enzyme-linked immunosorbent assay. Semi-thin sections of CA1 sections of the rat hippocampus were analyzed using the Image J. analysis program. The ultrastructural characteristics were studied using a PEM-100-01 transmission electron microscope (Selmi, Ukraine). Results and discussion. Long-term administration of isoniazid and rifampicin was associated with changes in the content of the cytosolic fraction of glial fibrillar acid protein obtained from the hippocampus. These changes were characterized by a tendency to increase the level of this protein by 17.8% (p=0.2) compared with intact animals. In contrast to the group of animals reproduced in the experiment drug-induced liver injury, in the experimental group, the level of glial fibrillar acid protein was significantly lower by 25.0% compared to the drug-induced liver injury group (p <0.05). Morphological analysis revealed a decrease in neuronal density in rats with drug-induced liver injury compared with intact control. At the same time, the specific number of degeneratively altered neurons in comparison with intact control in the group of drug-induced liver injury animals increased by 8.57 times. The number of degeneratively altered neurons in the group receiving yogurt / lactulose was 55.87 ± 4.23%, which was significantly higher than intact control rats, but was 19.4% (p <0.05) lower levels in rats with MIUP. Electron microscopic examination of rat hippocampal neuroglia was based on the study of changes in the astrocytic and oligodendroglial components. Changes in rat hippocampal neuroglia under experimental conditions were mainly related to the astrocytic link. Astrocytes were characterized by significantly lower cytoplasmic edema and adaptive-compensatory changes in the cell. Conclusion. Course administration of pro/prebiotics reduces the severity of manifestations of neurodegeneration, improves the state of astroglia in the hippocampus, and reduces the cytoplasmic levels of glial acidic fibrillar protein in animals with drug-induced liver injury

Keywords: probiotic, lactulose, drug-induced liver injury, hippocampus, glial fibrillar acid protein

Full text: PDF (Ukr) 1.58M

References
  1. Wang C, Fan RQ, Zhang YX, Nie H, Li K. Naringenin protects against isoniazid- and rifampicin-induced apoptosis in hepatic injury. World J Gastroenterol. 2016;22(44):9775-9783. https://www.ncbi.nlm.nih.gov/pubmed/27956801. PMCid: PMC5124982. https://doi.org/10.3748/wjg.v22.i44.9775
  2. Wang P, Pradhan K, Zhong XB, Ma X. Isoniazid metabolism and hepatotoxicity. Acta Pharmaceutica Sinica. 2016;6(5):384-392. https://www.ncbi.nlm.nih.gov/pubmed/27709007. PMCid: PMC5045547. https://doi.org/10.1016/j.apsb.2016.07.014
  3. Hakim Z, Waheed A, Bakhtiar S, Hasan N, Hakim B. Potentiating effect of rifampicin on methimazole induced hepatotoxicity in mice. Pakistan J Pharm Sci. 2018;31(6):2373-2377.
  4. Ridola L, Nardelli S, Gioia S, Riggio O. Quality of life in patients with minimal hepatic encephalopathy. World J Gastroenterol. 2018;24(48):5446-5453. https://www.ncbi.nlm.nih.gov/pubmed/30622374. PMCid: PMC6319138. https://doi.org/10.3748/wjg.v24.i48.5446
  5. Denisova EN. Porazheniya pecheni i ostraya pechenochnaya nedostatochnost' u bol'ny'kh s zabolevaniyami sistemy' krovi [Liver damage and acute liver failure in patients with diseases of the blood system]. Gematol Transfuziol. 2013;5(2):40-46. [Russian]
  6. Verdi S, Jackson MA, Beaumont M, Bowyer R, Bell JT, Spector TD, et al. An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health. Frontiers Aging Neurosci. 2018;10:398. https://www.ncbi.nlm.nih.gov/pubmed/30564113. PMCid: PMC6288358. https://doi.org/10.3389/fnagi.2018.00398
  7. Smirnov AV, Krayushkin AI, Gorelik EV, Gurov DYu, Grigoreva NV, Zamaraev VS, i dr. Morfologicheskaya kharakteristika gippokampa pri czerebral'nom ateroskleroze [Morphological characteristics of the hippocampus in cerebral atherosclerosis]. Sovr Probl Nauki Obrazovan. 2012;1. [Russian]
  8. Assonov DO, Bozhuk BS. Role of the hippocampus in memory functioning: modern view. Zaporozhye Med J. 2017;6:833-838. https://doi.org/10.14739/2310-1210.2017.6.115318
  9. Gomazkov OA. Astroczity' kak posredniki integraczionny'kh proczessov v mozge [Astrocytes as mediators of integration processes in the brain]. Uspekhi Sovr Biol. 2018;4:373-382. [Russian]
  10. Gomazkov OA. Astroczity' kak komponenty' regulyaczii vy'sshikh funkczij mozga [Astrocytes as components of the regulation of higher brain functions]. Nejrokhimiya. 2019;4:267-274. [Russian]
  11. Kovalchuk YuP, Ushakova HO. Rozpodil hlialnoho fibryliarnoho kysloho proteinu v riznykh viddilakh holovnoho mozku pishchanok pid chas rozvytku, starinnia ta dii alfa-ketohlutaratu [The distribution of glial fibrillar acidic protein in different parts of the brain of gerbils during the development, aging and action of alpha-ketoglutarate]. Med Klin Khimiia. 2016;1:29-35. [Ukrainian]
  12. Chorna VI, Lianna OL. Vplyv malykh doz ionizyvnoho vyprominennia na marker astrohlialnoi populiatsii klityn holovnoho mozku (eksperym doslidzh) [Influence of small doses of ionizing radiation on a marker of astroglial population of brain cells (experimental research)]. Ukr Radiol Zhurn. 2011;2:238-242. [Ukrainian]
  13. Kyrychenko S, Prishchepa I, Lagoda V, Velika M, Nedzvetsky V. Neyroprotektorni efekty α-lipoyevoyi kysloty na rozvytok okysnogo stresu y astrogliozu u mozku STZ-diabetychnykh shchuriv [Neuroprotective effects of α-lipoic acid on the development of oxidative stress and astrogliosis in the brain of STZ-diabetic rats]. Regulatory Mechanisms in Biosystems. 2014;5(2):143-147. [Ukrainian]. https://doi.org/10.15421/021427
  14. Drozdov AL, Chernaya VI. Nejrospeczificheskie belki GFKB i NCAM gippokampa pri formirovanii e'ngramm uslovno-reflektornoj pamyati [Neurospecific proteins GFАР and NCAM of the hippocampus in the formation of engrams of conditioned reflex memory]. Nejrokhimiya. 2006;1:47-51. [Russian]
  15. Butler MI, Cryan JF, Dinan TG. Man and the Microbiome: A New Theory of Everything? Annu Rev Clin Psychol. 2019;15:371-398. https://www.ncbi.nlm.nih.gov/pubmed/30786244. https://doi.org/10.1146/annurev-clinpsy-050718-095432
  16. Namasivayam S, Maiga M, Yuan W, Thovarai V, Costa DL, Mittereder LR, et al. Longitudinal profiling reveals a persistent intestinal dysbiosis triggered by conventional anti-tuberculosis therapy. Microbiome. 2017;5(1):71. https://www.ncbi.nlm.nih.gov/pubmed/28683818. PMCid: PMC5501520. https://doi.org/10.1186/s40168-017-0286-2
  17. Wipperman MF, Fitzgerald DW, Juste MAJ, Taur Y, Namasivayam S, Sher A, et al. Antibiotic treatment for Tuberculosis induces a profound dysbiosis of the microbiome that persists long after therapy is completed. Sci Rep. 2017;7:10767. https://www.ncbi.nlm.nih.gov/pubmed/28883399. PMCid: PMC5589918. https://doi.org/10.1038/s41598-017-10346-6
  18. Tripathi A, Debelius J, Brenner DA, Karin M, Loomba R, Schnabl B, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol. 2018;15:397-411. https://www.ncbi.nlm.nih.gov/pubmed/29748586. PMCid: PMC6319369. https://doi.org/10.1038/s41575-018-0011-z
  19. Milosevic I, Vujovic A, Barac A, Djelic M, Korac M, Radovanovic Spurnic A, et al. Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature. Int J Mol Sci. 2019;20(2):395. https://www.ncbi.nlm.nih.gov/pubmed/30658519. PMCid: PMC6358912. https://doi.org/10.3390/ijms20020395
  20. Bajaj JS, Heuman DM, Hylemon PB, Sanyal AJ, White MB, Monteith P, et al. Altered profile of human gut microbiome is associated with cirrhosis and its complications. J Hepatol. 2014;60:940-947. https://www.ncbi.nlm.nih.gov/pubmed/24374295. PMCid: PMC3995845. https://doi.org/10.1016/j.jhep.2013.12.019
  21. Wang HX, Wang YP. Gut Microbiota-brain Axis. Chinese Med J. 2016;129(19):2373-2380. https://www.ncbi.nlm.nih.gov/pubmed/27647198. PMCid: PMC5040025. https://doi.org/10.4103/0366-6999.190667
  22. Council Directive 2010/63/EU of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Communities. 2010.
  23. Dobrelia NV, Strielkov YeV, Bukhtiarova TA. Rozvytok yevropeiskoho zakonodavstva v sferi vykorystannia tvaryn u naukovykh eksperymentakh [Development of European legislation in the field of the use of animals in scientific experiments]. Farmakoloh Likar Toksykol. 2014;2(38):88-91. [Ukrainian]
  24. Berezhna LG, Kovalenko VM, Shayakhmetova GM, Voronina AK, Voloshyna OS. Gepatoprotektornyy efekt eksperymentalnoyi polivitaminnoyi kompozytsiyi za umov induktsiyi tsytokhromu R-450 2E1 izoniazydom i ryfampitsynom [The hepatoprotective effect of the experimental polyvitamin composition under the condition of the induction of cytochrome R-450 2e1 isoniazide and rifampicin]. Suchasni Probl Toksykol. 2005;3:54-58. [Ukrainian]
  25. Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nature Methods. 2012;7:671-675. https://www.ncbi.nlm.nih.gov/pubmed/22930834. PMCid: PMC5554542. https://doi.org/10.1038/nmeth.2089
  26. Nedzvetskyi VS. Stan hlialnykh promizhnykh filamentiv i zdatnist do navchannia u shchuriv pry eksperymentalnomu diabeti [The condition of glial intermediate filaments and the ability to learn in rats in experimental diabetes]. Fiziol Zh. 2004;1(50):85-90. [Ukrainian
  27. Fomenko OZ, Ushakova HO, Piierzhynovskyi SH. Proteiny astrohlii u mozku shchuriv za eksperymentalnoho khronichnoho hepatytuta dii 2 oksohlutaratu [Astroglial proteins in rat brain with experimental chronic hepatitis 2 oxoglutarate]. Ukr biokhim Zh. 2011;1(83):69-76. [Ukrainian]
  28. Ding JH, Jin Z, Yang XX, Lou J, Shan WX, Hu YX, et al. Role of gut microbiota via the gut-liver-brain axis in digestive diseases. World J Gastroenterol. 2020;26(40):6141-6162. https://www.ncbi.nlm.nih.gov/pubmed/33177790. PMCid: PMC7596643. https://doi.org/10.3748/wjg.v26.i40.6141
  29. Cryan JF, O'Riordan KJ, Cowan C, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877-2013. https://www.ncbi.nlm.nih.gov/pubmed/31460832. https://doi.org/10.1152/physrev.00018.2018
  30. Wang SZ, Yu YJ, Adeli K. Role of Gut Microbiota in Neuroendocrine Regulation of Carbohydrate and Lipid Metabolism via the Microbiota-Gut-Brain-Liver Axis. Microorganisms. 2020;8(4):527. https://www.ncbi.nlm.nih.gov/pubmed/32272588. PMCid: PMC7232453. https://doi.org/10.3390/microorganisms8040527