The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats
Authors
Ðurašević, SinišaRužičić, Aleksandra
Lakić, Iva
Tosti, Tomislav
Ðurović, Saša
Glumac, Sofija
Pejić, Snežana
Todorović, Ana
Drakulić, Dunja
Stanković, Sanja
Jasnić, Nebojša
Dević, Jelena Ð.
Todorović, Zoran B.
Article (Published version)
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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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords:
heart / inflammation / kidney / lipidomics / liver / oxidative stress / rats / sepsisSource:
International Journal of Molecular Sciences, 2022, 23, 4Publisher:
- MDPI
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200017 (University of Belgrade, Institute of Nuclear Sciences 'Vinča', Belgrade-Vinča) (RS-MESTD-inst-2020-200017)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200051 (Institute of General and Physical Chemistry, Belgrade) (RS-MESTD-inst-2020-200051)
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200110 (University of Belgrade, Faculty of Medicine) (RS-MESTD-inst-2020-200110)
DOI: 10.3390/ijms23042395
ISSN: 1422-0067
WoS: 000769724200001
Scopus: 2-s2.0-85124899800
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Ðurašević, Siniša AU - Ružičić, Aleksandra AU - Lakić, Iva AU - Tosti, Tomislav AU - Ðurović, Saša AU - Glumac, Sofija AU - Pejić, Snežana AU - Todorović, Ana AU - Drakulić, Dunja AU - Stanković, Sanja AU - Jasnić, Nebojša AU - Dević, Jelena Ð. AU - Todorović, Zoran B. PY - 2022 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5076 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. PB - MDPI 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 DO - 10.3390/ijms23042395 ER -
@article{ author = "Ðurašević, Siniša and Ružičić, Aleksandra and Lakić, Iva and Tosti, Tomislav and Ðurović, Saša and Glumac, Sofija and Pejić, Snežana and Todorović, Ana and Drakulić, Dunja and Stanković, Sanja and Jasnić, Nebojša and Dević, Jelena Ð. and Todorović, Zoran B.", 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. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.", publisher = "MDPI", 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", doi = "10.3390/ijms23042395" }
Ðurašević, S., Ružičić, A., Lakić, I., Tosti, T., Ðurović, S., Glumac, S., Pejić, S., Todorović, A., Drakulić, D., Stanković, S., Jasnić, N., Dević, J. Ð.,& Todorović, Z. B.. (2022). The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats. in International Journal of Molecular Sciences MDPI., 23(4). https://doi.org/10.3390/ijms23042395
Ðurašević S, Ružičić A, Lakić I, Tosti T, Ðurović S, Glumac S, Pejić S, Todorović A, Drakulić D, Stanković S, Jasnić N, Dević JÐ, Todorović ZB. 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). doi:10.3390/ijms23042395 .
Ðurašević, Siniša, Ružičić, Aleksandra, Lakić, Iva, Tosti, Tomislav, Ðurović, Saša, Glumac, Sofija, Pejić, Snežana, Todorović, Ana, Drakulić, Dunja, Stanković, Sanja, Jasnić, Nebojša, Dević, Jelena Ð., Todorović, Zoran B., "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), https://doi.org/10.3390/ijms23042395 . .