Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats

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dc.contributor.authorZvejniece, Liga
dc.contributor.authorSvalbe, Baiba
dc.contributor.authorVavers, Edijs
dc.contributor.authorOzola, Melita
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorGukalova, Baiba
dc.contributor.authorSevostjanovs, Eduards
dc.contributor.authorLiepinsh, Edgars
dc.contributor.authorDambrova, Maija
dc.contributor.institutionDepartment of Pharmaceutical Chemistry
dc.date.accessioned2023-11-23T11:15:01Z
dc.date.available2023-11-23T11:15:01Z
dc.date.issued2023-12
dc.descriptionPublisher Copyright: © 2023 The Authors
dc.description.abstractLong-chain acylcarnitines (LCACs) are intermediates of fatty acid oxidation and are known to exert detrimental effects on mitochondria. This study aimed to test whether lowering LCAC levels with the anti-ischemia compound 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB) protects brain mitochondrial function and improves neurological outcomes after transient middle cerebral artery occlusion (MCAO). The effects of 14 days of pretreatment with methyl-GBB (5 mg/kg, p.o.) on brain acylcarnitine (short-, long- and medium-chain) concentrations and brain mitochondrial function were evaluated in Wistar rats. Additionally, the mitochondrial respiration and reactive oxygen species (ROS) production rates were determined using ex vivo high-resolution fluorespirometry under normal conditions, in models of ischemia-reperfusion injury (reverse electron transfer and anoxia-reoxygenation) and 24 h after MCAO. MCAO model rats underwent vibrissae-evoked forelimb-placing and limb-placing tests to assess neurological function. The infarct volume was measured on day 7 after MCAO using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Treatment with methyl-GBB significantly reduced the LCAC content in brain tissue, which decreased the ROS production rate without affecting the respiration rate, indicating an increase in mitochondrial coupling. Furthermore, methyl-GBB treatment protected brain mitochondria against anoxia–reoxygenation injury. In addition, treatment with methyl-GBB significantly reduced the infarct size and improved neurological outcomes after MCAO. Increased mitochondrial coupling efficiency may be the basis for the neuroprotective effects of methyl-GBB. This study provides evidence that maintaining brain energy metabolism by lowering the levels of LCACs protects against ischemia-induced brain damage in experimental stroke models.en
dc.description.statusPeer reviewed
dc.format.extent1014874
dc.identifier.citationZvejniece, L, Svalbe, B, Vavers, E, Ozola, M, Grinberga, S, Gukalova, B, Sevostjanovs, E, Liepinsh, E & Dambrova, M 2023, 'Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats', Biomedicine and Pharmacotherapy, vol. 168, 115803. https://doi.org/10.1016/j.biopha.2023.115803
dc.identifier.doi10.1016/j.biopha.2023.115803
dc.identifier.issn0753-3322
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/14979
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85175475759&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofBiomedicine and Pharmacotherapy
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectIschemic stroke
dc.subjectLong-chain acylcarnitines
dc.subjectMCAO
dc.subjectMethyl-GBB
dc.subjectROS
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectPharmacology
dc.titleDecreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in ratsen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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