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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.<\/jats:p>","DOI":"10.3390\/ijms23042395","type":"journal-article","created":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:47:45Z","timestamp":1645476465000},"page":"2395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Effects of a Meldonium Pre-Treatment on the Course of the LPS-Induced Sepsis in Rats"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4406-8376","authenticated-orcid":false,"given":"Sini\u0161a","family":"\u0110ura\u0161evi\u0107","sequence":"first","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0590-8248","authenticated-orcid":false,"given":"Aleksandra","family":"Ru\u017ei\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8894-7300","authenticated-orcid":false,"given":"Iva","family":"Laki\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1403-4688","authenticated-orcid":false,"given":"Tomislav","family":"Tosti","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2022-2447","authenticated-orcid":false,"given":"Sa\u0161a","family":"\u0110urovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of General and Physical Chemistry, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofija","family":"Glumac","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4573-2371","authenticated-orcid":false,"given":"Sne\u017eana","family":"Peji\u0107","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences\u2014National Institute of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-1637","authenticated-orcid":false,"given":"Ana","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences\u2014National Institute of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Drakuli\u0107","sequence":"additional","affiliation":[{"name":"Vin\u010da Institute of Nuclear Sciences\u2014National Institute of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-535X","authenticated-orcid":false,"given":"Sanja","family":"Stankovi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Medical Biochemistry, University Clinical Centre of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medical Sciences, University of Kragujevac, 550601 Kragujevac, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0333-333X","authenticated-orcid":false,"given":"Neboj\u0161a","family":"Jasni\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"\u0110or\u0111evi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8869-9976","authenticated-orcid":false,"given":"Zoran","family":"Todorovi\u0107","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"University Medical Centre \u201cBe\u017eanijska Kosa\u201d, 11080 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Shrum, B., Anantha, R.V., Xu, S.X., Donnelly, M., Haeryfar, S.M., McCormick, J.K., and Mele, T. 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