Delayed effects of antibiotic therapy in endotoxinemia (experimental study)



Cite item

Full Text

Abstract

Nowadays, due to the increasing number of infectious and inflammatory diseases, the problem of the use of antibacterial drugs becomes especially important. As a result of the action of toxins, inflammatory processes can affect the central nervous system with the subsequent development of neuroinflammation. Activation of neuroinflammation leads to dysregulation of many physiological functions. These negative appearances can be observed even after a long period. It is known that doxycycline is a tetracycline–type antibiotic, which is able to penetrate the blood-brain barrier and has anti-inflammatory activity. The aim of this study was to investigate the nature of delayed physiological changes in rats against the background of administration of the antibacterial drug doxycycline in the LPS-induced model of neuroinflammation. Four groups of Wistar rats, 10 males in each group, were used in the experiment. The first group was injected once intraperitoneally with physiological solution, the second group - with LPS (1 mg/kg). Animals of the third and fourth groups received intragastrically doxycycline solution (25 mg/kg) daily for two weeks. On the 15th day of the experiment, rats from the fourth group were injected with LPS (1 mg/kg). Body weight of animals, mass coefficients of immunocompetent organs, as well as behaviour and motor activity of rats in the «Open Field» test were evaluated at several time points. It was shown that systemic injection of LPS led to an increase in the mass coefficients of spleen, kidneys and adrenal glands compared to the group of animals receiving doxycycline beforehand. These changes were noted 48 h and 2 months after the injection of endotoxin. In the «Open Field» test, animals that were injected with doxycycline and LPS showed no violations of motor activity and research behavior, unlike the group that received only LPS. It can be assumed that the physiological effects of doxycycline in the LPS-induced model of neuroinflammation revealed at early and late terms are not limited to the antibacterial effect of the drug and are mediated by anti-inflammatory and potential neuroprotective effects on the central nervous system.

Full Text

Restricted Access

References

  1. Kent S, Bluthé RM, Kelley KW, Dantzer R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci. 1992;13(1):24-28. https://doi.org/10.1016/0165-6147(92)90012-u.
  2. Ascherio A, Schwarzschild MA. The epidemiology of Parkinson's disease: risk factors and prevention. Lancet Neurol. 2016;15(12):1257-1272. https://doi.org/10.1016/S1474-4422(16)30230-7.
  3. Moyse E, Krantic S, Djellouli N, et al. Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases. Front Aging Neurosci. 2022;14:827263. Published 2022 May 19. https://doi.org/10.1016/S1474-4422(16)30230-7.
  4. Lazzarini M, Martin S, Mitkovski M, et al. Doxycycline restrains glia and confers neuroprotection in a 6-OHDA Parkinson model. Glia. 2013;61(7):1084-1100. https://doi.org/10.1002/glia.22496.
  5. Zhang JC, Yao W, Dong C, et al. Blockade of interleukin-6 receptor in the periphery promotes rapid and sustained antidepressant actions: a possible role of gut-microbiota-brain axis. Transl Psychiatry. 2017;7(5):e1138. Published 2017 May 30. https://doi.org/10.1038/tp.2017.112.
  6. Balducci C, Santamaria G, La Vitola P, et al. Doxycycline counteracts neuroinflammation restoring memory in Alzheimer's disease mouse models. Neurobiol Aging. 2018;70:128-139. https://doi.org/10.1016/j.neurobiolaging.2018.06.002.
  7. Mello BS, Monte AS, McIntyre RS, et al. Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. Journal of Psychiatric Research. 2013;47(10):1521-1529. https://doi.org/10.1016/j.jpsychires.2013.06.008.
  8. The procedure for testing animals in the "Open field": [Electronic resource]. URL: https://www.openscience.ru/index.php?article=001 (date of request: 04.2024).
  9. Chaskiel L, Bristow AD, Bluthé RM, et al. Interleukin-1 reduces food intake and body weight in rat by acting in the arcuate hypothalamus. Brain, behavior, and immunity. 2019;81:560-573. https://doi.org/10.1016/j.bbi.2019.07.017.
  10. Borges Bde C, Rorato RC, Uchoa ET, et al. Protein tyrosine phosphatase-1B contributes to LPS-induced leptin resistance in male rats. American journal of physiology. Endocrinology and metabolism. 2015;308(1):E40-E50. https://doi.org/10.1152/ajpendo.00094.2014.
  11. Yrjänheikki J, Keinänen R, Pellikka M, Hökfelt T, Koistinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A. 1998;95(26):15769-15774. https://doi.org/10.1073/pnas.95.26.15769.
  12. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005;27(9):1329-1342. https://doi.org/10.1016/j.clinthera.2005.09.005.
  13. Konev Yu V. The role of endotoxin (LPS) in the pathogenesis of metabolic syndrome and atherosclerosis // EiKG. 2012. N.11 URL: https://cyberleninka.ru/article/n/rol-endotoksina-lps-v-patogeneze-metabolicheskogo-sindroma-i-ateroskleroza (date of request: 04.2024).
  14. Badshah H, Ali T, Kim MO. Osmotin attenuates LPS-induced neuroinflammation and memory impairments via the TLR4/NFκB signaling pathway. Scientific reports. 2016;6:24493. Published 2016 Apr 20. https://doi.org/10.1038/srep24493.
  15. Xiao K, Zou WH, Yang Z, et al. The role of visfatin on the regulation of inflammation and apoptosis in the spleen of LPS-treated rats. Cell and tissue research. 2015;359(2):605-618. https://doi.org/10.1007/s00441-014-1997-3.
  16. Deng Z, Yan S, Hu H, et al. Proteomic profile of carbonylated proteins in rat liver: discovering possible mechanisms for tetracycline-induced steatosis. Proteomics. 2015;15(1):148-159. https://doi.org/10.1002/pmic.201400115.
  17. Varma S, Nathanson J, Dowlatshahi M, et al. Doxycycline-induced cholestatic liver injury. Clin J Gastroenterol. 2021;14(5):1503-1510. https://doi.org/10.1007/s12328-021-01475-7.
  18. Shishkina GT, Lanshakov DA, Bannova AV, et al. Doxycycline Used for Control of Transgene Expression has its Own Effects on Behaviors and Bcl-xL in the Rat Hippocampus. Cell Mol Neurobiol. 2018;38(1):281-288. https://doi.org/10.1007/s10571-017-0545-6.
  19. Shishkina GT, Bannova AV, Komysheva NP, Dygalo NN. Doxycycline attenuates anxiety and microglia activation induced by repeated lipopolysaccharide. European Neuropsychopharmacology. 2019;29:179-180. https://doi.org/10.1016/j.euroneuro.2019.09.276.
  20. Santa-Cecília FV, Socias B, Ouidja MO, et al. Doxycycline Suppresses Microglial Activation by Inhibiting the p38 MAPK and NF-kB Signaling Pathways. Neurotoxicity Research. 2016;29(4):447-459. https://doi.org/10.1007/s12640-015-9592-2

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) Eco-Vector


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 74760 от 29.12.2018 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies