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The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats

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2022
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Authors
Đurašević, Siniša
Ružičić, Aleksandra
Lakić, Iva
Tosti, Tomislav
Đurović, Saša
Glumac, Sofija
Pejić, Snežana
Todorović, Ana
Drakulić, Dunja R.
Stanković, Sanja
Jasnić, Nebojša
Đorđević, Jelena
Todorović, Zoran
Article (Published version)
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© 2022 The Author(s)
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Abstract
A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcom...e the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.

Keywords:
Heart / Inflammation / Kidney / Lipidomics / Liver / Oxidative stress / Rats / Sepsis
Source:
International Journal of Molecular Sciences, 2022, 23, 4, 2395-
Funding / projects:
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200178 (University of Belgrade, Faculty of Biology) (RS-200178)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) (RS-200017)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200168 (University of Belgrade, Faculty of Chemistry) (RS-200168)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200051 (Institute of General and Physical Chemistry, Belgrade) (RS-200051)
  • Ministry of Education, Science and Technological Development, Republic of Serbia, Grant no. 200110 (University of Belgrade, Faculty of Medicine) (RS-200110)

DOI: 10.3390/ijms23042395

ISSN: 1661-6596

WoS: 000769724200001

Scopus: 2-s2.0-85124899800
[ Google Scholar ]
4
URI
https://vinar.vin.bg.ac.rs/handle/123456789/10173
Collections
  • Radovi istraživača
Institution/Community
Vinča
TY  - JOUR
AU  - Đurašević, Siniša
AU  - Ružičić, Aleksandra
AU  - Lakić, Iva
AU  - Tosti, Tomislav
AU  - Đurović, Saša
AU  - Glumac, Sofija
AU  - Pejić, Snežana
AU  - Todorović, Ana
AU  - Drakulić, Dunja R.
AU  - Stanković, Sanja
AU  - Jasnić, Nebojša
AU  - Đorđević, Jelena
AU  - Todorović, Zoran
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10173
AB  - A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.
T2  - International Journal of Molecular Sciences
T1  - The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats
VL  - 23
IS  - 4
SP  - 2395
DO  - 10.3390/ijms23042395
ER  - 
@article{
author = "Đurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Đurović, Saša and Glumac, Sofija and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja R. and Stanković, Sanja and Jasnić, Nebojša and Đorđević, Jelena and Todorović, Zoran",
year = "2022",
abstract = "A dysregulated and overwhelming response to an infection accompanied by the exaggerated pro-inflammatory state and metabolism disturbance leads to the fatal outcome in sepsis. Previously we showed that meldonium, an anti-ischemic drug clinically used to treat myocardial and cerebral ischemia, strongly increases mortality in faecal-induced peritonitis (FIP) in rats. We postulated that the same mechanism that is responsible for the otherwise strong anti-inflammatory effects of meldonium could be the culprit of the increased mortality. In the present study, we applied the LPS-induced model of sepsis to explore the presence of any differences from and/or similarities to the FIP model. When it comes to energy production, despite some shared similarities, it is evident that LPS and FIP models of sepsis differ greatly. A different profile of sympathoadrenal activation may account for this observation, as it was lacking in the FIP model, whereas in the LPS model it was strong enough to overcome the effects of meldonium. Therefore, choosing the appropriate model of sepsis induction is of great importance, especially if energy homeostasis is the main focus of the study. Even when differences in the experimental design of the two models are acknowledged, the role of different patterns of energy production cannot be excluded. On that account, our results draw attention to the importance of uninterrupted energy production in sepsis but also call for much-needed revisions of the current recommendations for its treatment.",
journal = "International Journal of Molecular Sciences",
title = "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats",
volume = "23",
number = "4",
pages = "2395",
doi = "10.3390/ijms23042395"
}
Đurašević, S., Ružičić, A., Lakić, I., Tosti, T., Đurović, S., Glumac, S., Pejić, S., Todorović, A., Drakulić, D. R., Stanković, S., Jasnić, N., Đorđević, J.,& Todorović, Z.. (2022). The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences, 23(4), 2395.
https://doi.org/10.3390/ijms23042395
Đurašević S, Ružičić A, Lakić I, Tosti T, Đurović S, Glumac S, Pejić S, Todorović A, Drakulić DR, Stanković S, Jasnić N, Đorđević J, Todorović Z. The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences. 2022;23(4):2395.
doi:10.3390/ijms23042395 .
Đurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Đurović, Saša, Glumac, Sofija, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja R., Stanković, Sanja, Jasnić, Nebojša, Đorđević, Jelena, Todorović, Zoran, "The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats" in International Journal of Molecular Sciences, 23, no. 4 (2022):2395,
https://doi.org/10.3390/ijms23042395 . .

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