Lviv clinical bulletin 2023, 3(43)-4(44): 45-51

https://doi.org/10.25040/lkv2023.03-04.045

Endothelin-1 indices in patients with leptospirosis of various severity degrees and their changes under the influence of seven-day treatment

Posted onAuthorAdminЗалишити коментар / Leave a comment

T. Telehina, O. Zinchuk

Danylo Halytsky Lviv National Medical University

Introduction. Leptospirosis is one of the most common zoonoses in the world, pathogenesis of which is based on the damage of vascular endothelium. Violation of endothelial functions leads to damage of these cells plasma membranes, loss of vascular integrity, ischemia, necrosis, and, finally, the development of organ dysfunction. In current literature there is sparce information concerning endothelial dysfunction in patients with leptospirosis, therefore the development and standardization of methods for the assessment of vascular endothelium imbalance in patients with leptospirosis of different severity degrees is an urgent task. Detection of endothelin-1 (ET-1) one of the best markers of endothelial dysfunction, can become an important tool for predicting the severity of the disease.

The aim of the study. To investigate ET-1 indices in patients with leptospirosis of different severity degrees and to estimate their changes after the seven-day treatment.

Materials and methods. ET-1 content in the blood serum of patients with diagnosed leptospirosis was detected by ELISA method. Absolute values were compared using Mann-Whitney test (U-test); the results were statistically processed using Fisher’s bilateral test (F-test). Correlation analysis was carried out according to Spearman’s method. The difference was considered statistically significant with p < 0.05.

Results. ET-1 content was detected at time of hospitalization and after 7 days of leptospirosis treatment. Patients (n = 43) were divided into two groups depending on the severity of leptospirosis course: the first group with a moderate course included 21 patients; second group with a severe course included 22 patients; the control group consisted of 20 healthy individuals. Both groups of leptospirosis affected patients demonstrated significantly higher ET-1 concentration in comparison with the control group (p < 0.01). Moreover, the proportion of patients with high (> 5.5 pg/ml) concentration of ET-1 in the blood post the 7 days treatment was documented in 13.3% patients of the first group, and 43.8% patients of the second group (p < 0.05). It was also estimated that in both groups patients 7 days treatment of leptospirosis induced a credible increase in the concentration of ET-1 (p < 0.05).

Conclusions. Our results claim that at time of hospitalization and after 7 days treatment both groups of leptospirosis affected patients demonstrated significantly higher level of ET-1 in comparison to control group individuals (p < 0.01). 7 days of leptospirosis treatment caused a credible enhancement of ET-1 content (p < 0.05). Patients with a severe course of leptospirosis after 7 days treatment exposed significantly higher ET-1 concentration compared to patients with moderate course (p < 0.05).

References

  1. Vasilieva NA, Andreychin MA. Ternopil: Ukrmedknyha; 2016. 275 р. (Ukrainian)
  2. Abraham GR, Kuc RE, Althage M, Greasley PJ, Ambery P, Maguire JJ et al. Endothelin-1 is increased in the plasma of patients hospitalised with Covid-19. J Mol Cell Cardiol. 2022;167:92-96. https://doi.org/10.1016/j.yjmcc.2022.03.007
  3. Bouallegue A, Daou GB, Srivastava AK. Endothelin-1-induced signaling pathways in vascular smooth muscle cells. Curr Vasc Pharmacol. 2007;5(1):45-52. https://doi.org/10.2174/157016107779317161
  4. Calvopiña M, Vásconez E, Coral-Almeida M, Romero-Alvarez D, Garcia-Bereguiain MA, Orlando A. Leptospirosis: Morbidity, mortality, and spatial distribution of hospitalized cases in Ecuador. A nationwide study 2000-2020. PLoS Negl Trop Dis. 2022;16(5):e0010430. https://doi.org/10.1371/journal.pntd.0010430
  5. Cerutti C, Ridley AJ. Endothelial cell-cell adhesion and signaling. Exp Cell Res. 2017;358(1):31-38. https://doi.org/10.1016/j.yexcr.2017.06.003
  6. Costa ACTRB, Pereira CR, Sáfadi T, Heinemann MB, Dorneles EMS. Climate influence the human leptospirosis cases in Brazil, 2007-2019: A time series analysis. Trans R Soc Trop Med Hyg. 2022;116(2):124-132. https://doi.org/10.1093/trstmh/trab092
  7. De Brito T, Silva AMG da, Abreu PAE. Pathology and pathogenesis of human leptospirosis: A commented review. Rev Inst Med Trop Sao Paulo. 2018;60:e23. https://doi.org/10.1590/s1678-9946201860023
  8. Freeman BD, Machado FS, Tanowitz HB, Desruisseaux MS. Endothelin-1 and its role in the pathogenesis of infectious diseases. Life Sci. 2014;118(2):110-119. https://doi.org/10.1016/j.lfs.2014.04.021
  9. Goeijenbier M, Gasem MH, Meijers JCM, Hartskeerl RA, Ahmed A, Goris MGA et al. Markers of endothelial cell activation and immune activation are increased in patients with severe leptospirosis and associated with disease severity. J Infect. 2015;71(4):437-446. https://doi.org/10.1016/j.jinf.2015.05.016
  10. Hirase T, Node K. Endothelial dysfunction as a cellular mechanism for vascular failure. Am J Physiol Heart Circ Physiol. 2012;302(3):H499-505. https://doi.org/10.1152/ajpheart.00325.2011
  11. Libório AB, Braz MBM, Seguro AC, Meneses GC, Neves FM de O, Pedrosa DC et al. Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury. Am J Trop Med Hyg. 2015;92(3):611-616. https://doi.org/10.4269/ajtmh.14-0232
  12. Lüscher TF, Barton M. Biology of the endothelium. Clin Cardiol. 1997;20(11 Suppl 2):II-3-10. https://doi.org/10.1002/j.1932-8737.1997.tb00006.x
  13. McCarron RM, Wang L, Stanimirovic DB, Spatz M. Endothelin induction of adhesion molecule expression on human brain microvascular endothelial cells. Neurosci Lett. 1993;156(1-2):31-34. https://doi.org/10.1016/0304-3940(93)90432-K
  14. Piechota M, Banach M, Irzmanski R, Barylski M, Piechota-Urbanska M, Kowalski J et al. Plasma endothelin-1 levels in septic patients. J Intensive Care Med. 2007;22(4):232-239. https://doi.org/10.1177/0885066607301444
  15. Raffray L, Giry C, Thirapathi Y, Reboux AH, Jaffar-Bandjee MC, Gasque P. Increased levels of soluble forms of E-selectin and ICAM-1 adhesion molecules during human leptospirosis. PLoS One. 2017;12(7):e0180474. https://doi.org/10.1371/journal.pone.0180474
  16. Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G et al. The vascular endothelium and human diseases. Int J Biol Sci. 2013;9(10):1057-1069. https://doi.org/10.7150/ijbs.7502
  17. Strand TM, Löhmus M, Persson Vinnersten T, Rаsbäck T, Sundström K, Bergström T et al. Highly Pathogenic Leptospira Found in Urban Brown Rats (Rattus norvegicus) in the Largest Cities of Sweden. Vector Borne Zoonotic Dis. 2015;15(12):779-781. https://doi.org/10.1089/vbz.2015.1800
  18. Sudulagunta SR, Sodalagunta MB, Kumbhat M, Settikere Nataraju A. Posterior reversible encephalopathy syndrome (PRES). Oxford Med Case Reports. 2017;2017(4):43-46. https://doi.org/10.1093/omcr/omx011
  19. Warnasekara J, Koralegedara I, Agampodi S. Estimating the burden of leptospirosis in Sri Lanka: A systematic review. BMC Infect Dis. 2019;19(1):119. https://doi.org/10.1186/s12879-018-3655-y