Please use this identifier to cite or link to this item:
10.1016/j.biopha.2023.115803
Title: | Decreased long-chain acylcarnitine content increases mitochondrial coupling efficiency and prevents ischemia-induced brain damage in rats |
Authors: | Zvejniece, Liga Svalbe, Baiba Vavers, Edijs Ozola, Melita Grinberga, Solveiga Gukalova, Baiba Sevostjanovs, Eduards Liepinsh, Edgars Dambrova, Maija Department of Pharmaceutical Chemistry |
Keywords: | Ischemic stroke;Long-chain acylcarnitines;MCAO;Methyl-GBB;ROS;3.1 Basic medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Pharmacology |
Issue Date: | Dec-2023 |
Citation: | Zvejniece , 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 |
Abstract: | Long-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. |
Description: | Publisher Copyright: © 2023 The Authors |
DOI: | 10.1016/j.biopha.2023.115803 |
ISSN: | 0753-3322 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
Files in This Item:
File | Size | Format | |
---|---|---|---|
Decreased_long-chain_acylcarnitine_content_increases_mitochondrial_coupling_efficiency.pdf | 991.09 kB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.