1887
Volume 2022 Number 3
  • ISSN: 1999-7086
  • EISSN: 1999-7094

Abstract

A cytokine storm is a serious clinical condition that complicates infectious diseases, for example, coronavirus disease 2019 (COVID-19), and non-infectious diseases such as autoimmune diseases and cancer and may often lead to death. The patients who are affected by the cytokine storm are almost always severe/critical and at risk for acute respiratory distress syndrome or eventually death. Pro-inflammatory cytokines such as interleukin 6 (IL-6), IL-1 beta, and tumor necrosis factor alpha (TNF-α) have been repeatedly shown to be related to the COVID-19 disease severity and mortality. In this study, our objective was to evaluate the attenuated effect of rivastigmine (RA) in a cytokine storm in Swiss Albino mice in which the cytokine storm was induced by lipopolysaccharide (LPS) and to explore their effects on IL-1 β, IL-6, and TNF-α levels. This study was carried with 60 male Swiss albino mice that were divided equally and randomly into six groups as follows:

  1. • Group AH: Apparently healthy control group which received no induction, not treated.
  2. • Group LPS: Induced using LPS at 5 mg/kg and no treatment administered.
  3. • Group DMSO: Induced and treated with 1% dimethyl sulfoxide (DMSO).
  4. • Group RA: Induced and treated with 0.5 mg/kg RA.
  5. • Group MPA: Induced and treated with 50 mg/kg methylprednisolone (MPA).
  6. • Group RMPA: Induced and treated with 0.25 mg/kg rivastigmine and 25 mg/kg of methylprednisolone.

All the mice were treated with drugs or vehicles for three consecutive days before LPS induction. The mice were then injected with LPS intraperitoneally at a dosage of 5 mg/kg for systematic inflammatory stimulation. After 48 hours of LPS induction, all the mice were euthanized by light anesthesia with chloroform, and blood was collected for the quantitative determination of IL-1β, IL-6, and TNF-α levels using the enzyme-linked immunosorbent assay (ELISA) technique. Administration of LPS to Swiss albino mice caused a significant elevation of IL-1β, IL-6, and TNF-α levels than in the healthy control group. Significant reduction of these parameters were observed in the RA and MPA groups when compared with those in the non-treated group. RA was found to be effective in attenuating the induced cytokine storm by suppressing IL-1β, IL-6, and TNF-α levels, and the results with RA were comparable to that of MPA. A combination of half-doses of both RA and MPA administered together shows no obvious advantage when compared with that of each of them alone.

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2022-06-06
2024-03-28
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References

  1. Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, et al. Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper. Front Immunol. 2020 Jul 10;:11:1648.
    [Google Scholar]
  2. Shimabukuro-Vornhagen A, Gödel P, Subklewe M, Stemmler HJ, Schlößer HA, Schlaak M, Kochanek M, Böll B, von Bergwelt-Baildon MS. Cytokine release syndrome. J Immunother Cancer. 2018;:6:56.
    [Google Scholar]
  3. Sun X, Wang T, Cai D, et al. Cytokine storm intervention in the early stages of COVID-19 pneumonia. Cytokine Growth Factor Rev. 2020;53:38–42.
    [Google Scholar]
  4. Kounis NG, Soufras GD, Hahalis G. Anaphylactic cardiac collapse, sudden death, and the Kounis syndrome. J Postgrad Med. 2014;:60:227–9.
    [Google Scholar]
  5. Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, Komanduri KV, Lin Y, Jain N, Daver N. Chimeric antigen receptor T-cell therapy-assessment and management of toxicities. Nat Rev Clin Oncol. 2018;:15:47–62.
    [Google Scholar]
  6. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;:323:1061–9.
    [Google Scholar]
  7. Sunkara H, Dewan SMR. Coronavirus disease-2019: A review on the disease exacerbation via cytokine storm and concurrent management. Int Immunopharmacol. 2021;:99:108049.
    [Google Scholar]
  8. Ahmad F. COVID-19 induced ARDS, and the use of galantamine to activate the cholinergic anti-inflammatory pathway. Med Hypotheses. 2020;:145:110331.
    [Google Scholar]
  9. Udit S, Blake K, Chiu IM. Somatosensory and autonomic neuronal regulation of the immune response. Nature Reviews Neuroscience. 2022;:23:157–71.
    [Google Scholar]
  10. Enz A, Gentsch C. Co-administration of memantine does not affect the in vitro, or ex vivo determined acetylcholinesterase inhibition of rivastigmine in the rat brain. Neuropharm. 2004; 47:(3):408–13.
    [Google Scholar]
  11. Marucci G, Buccioni M, Ben DD, Lambertucci C, Volpini R, Amenta F. Efficacy of acetylcholinesterase inhibitors in Alzheimer's disease. Neuropharm. 2021;:190:108352.
    [Google Scholar]
  12. Daniel WW, Cross CL. Biostatistics: a foundation for analysis in the health sciences. Wiley; 2018.
    [Google Scholar]
  13. Mohammed A. In lipopolysaccharide-induced sepsis. Department of Immunology; 2016.
    [Google Scholar]
  14. Shao C, Lin S, Liu S, Jin P, Lu W, Li N, et al. HIF1α-induced glycolysis in macrophage is essential for the protective effect of ouabain during endotoxemia. Oxid Med Cell Longev. 2019;:2019:7136585.
    [Google Scholar]
  15. Hashimoto R, Kakigi R, Miyamoto Y, Nakamura K, Itoh S, Daida H, et al. JAK-STAT-dependent regulation of scavenger receptors in LPS-activated murine macrophages. Eur J Pharmacol. 2020;:871:172940. doi: 10.1016/j.ejphar.2020.172940.
    [Google Scholar]
  16. Park WJ, Han JS. Gryllus bimaculatus extract protects against lipopolysaccharide and palmitate-induced production of proinflammatory cytokines and inflammasome formation. Mol Med Rep. 2021; 23:(3):1–10.
    [Google Scholar]
  17. Zumla A, Wang F-S, Ippolito G, et al. Reducing mortality and morbidity in patients with severe COVID-19 disease by advancing ongoing trials of Mesenchymal Stromal (stem) cell (MSC) therapy—achieving global consensus and visibility for cellular host-directed therapies. Int J Infect Dis. 2020;:96:431–9.
    [Google Scholar]
  18. Rabaan AA, Al-Ahmed SH, Muhammad J, et al. Role of inflammatory cytokines in COVID-19 patients: a review on molecular mechanisms, immune functions, immunopathology and immunomodulatory drugs to counter cytokine storm.” Vaccines 2021; 9:(5):436.
    [Google Scholar]
  19. Gubandru M, Margina D, Tsitsimpikou C, Goutzourelas N, Tsarouhas K, Ilie M, et al. Alzheimer's treated patients showed different patterns for oxidative stress and inflammation markers. Food Chem Toxicol. 2013;:61:209–14. doi: 10.1016/j.fct.2013.07.013.
    [Google Scholar]
  20. Lin S, Wu H, Wang C, Xiao Z, and Xu F. Regulatory T cells and acute lung injury: Cytokines, uncontrolled inflammation, and therapeutic implications. Front Immunol. 2018;:9:1545.
    [Google Scholar]
  21. Alonge O, Iqbal FM, Cifonelli E. Collapse in the elderly: rivastigmine-induced heart block and a literature review of the pharmacology of acetylcholinesterase inhibitors used in Alzheimer's disease. Case Rep. 2018;:2018:bcr-2018-224597.
    [Google Scholar]
  22. Khuanjing T, Palee S, Chattipakorn SC, Chattipakorn N. The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports. Acta Physiol. 2020; 228:(2):e13396.
    [Google Scholar]
  23. Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000; 405:(6785):458–62. doi: 10.1038/35013070.
    [Google Scholar]
  24. Yi Y, Yan P, Jin Y. Galantamine protects against hydrochloric acid aspiration induced acute respiratory distress syndrome in rabbits. Trop J Pharm Res. doi: 10.4314/tjpr.v17i4.15.
    [Google Scholar]
  25. Wazea SA, Wadie W, Bahgat AK, et al. Galantamine anti-colitic effect: Role of alpha-7 nicotinic acetylcholine receptor in modulating Jak/STAT3, NF κB/HMGB1/RAGE and p-AKT/Bcl-2 pathways. Sci Rep. 2018;:8:5110. doi: 10.1038/s41598-018-23359-6.
    [Google Scholar]
  26. Liu Z-H, Ma Y-F, Wu J-S, Gan J-X, Xu S-W, Jiang GY. Effect of cholinesterase inhibitor galanthamine on circulating tumor necrosis factor alpha in rats with lipopolysaccharide-induced peritonitis. Cin Med J (Engl). 2010; 123:(13):1727–30.
    [Google Scholar]
  27. Sadiq AT, Zalzala MH. The Possible Protective Effect of Safranal on the Lipopolysaccharide-induced Acute Lung Injury in Mice. Int J Drug Del Technol. 2021; 11:(3):771–6.
    [Google Scholar]
  28. Yang Y, Li L. Depleting microRNA-146a-3p attenuates lipopolysaccharide-induced acute lung injury via up-regulating SIRT1 and mediating NF-κB pathway. J Drug Target. 2021; 29:(4):420–9.
    [Google Scholar]
  29. Lu Z, Xie P, Zhang D, et al. 3-Dehydroandrographolide protects against lipopolysaccharide-induced inflammation through the cholinergic anti-inflammatory pathway. Biochem Pharmacol. 2018;:158:305–17.
    [Google Scholar]
  30. Tian J, Han T, Pan M. Friedelin protects against alveolar epithelial cells apoptosis in Lps-induced acute pneumonia in neonatal rats by suppressing NF-κB activation. Curr Top Nutraceutical Res. 2021; 19:(1):58–63.
    [Google Scholar]
  31. Hu B, Yan L-F, Sun Q, et al. Disturbed neurovascular coupling in type 2 diabetes mellitus patients: evidence from a comprehensive fMRI analysis. NeuroImage Clin. 2019;:22:101802.
    [Google Scholar]
  32. Yatawara C, Zailan FZ, Chua EV, et al. The efficacy of transdermal rivastigmine in mild to moderate Alzheimer's disease with concomitant small vessel cerebrovascular disease: findings from an open-label study. Clin Interv Aging. 2021;:16:301–9.
    [Google Scholar]
  33. Wilczynska J, Pfeil U, Zakrzewicn A, et al. Acetylcholine and chronic vasculopathy in rat renal allografts. Transplantation. 2011; 91:(3):263–70.
    [Google Scholar]
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