Decrease in Long-Chain Acylcarnitine Tissue Content Determines the Duration of and Correlates with the Cardioprotective Effect of Methyl-GBB

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dc.contributor.authorKuka, Janis
dc.contributor.authorMakrecka-Kuka, Marina
dc.contributor.authorCirule, Helena
dc.contributor.authorGrinberga, Solveiga
dc.contributor.authorSevostjanovs, Eduards
dc.contributor.authorDambrova, Maija
dc.contributor.authorLiepinsh, Edgars
dc.contributor.institutionFaculty of Pharmacy
dc.date.accessioned2021-05-11T13:10:01Z
dc.date.available2021-05-11T13:10:01Z
dc.date.issued2017-08
dc.descriptionPublisher Copyright: © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
dc.description.abstractIschaemia in the heart is accompanied by the accumulation of long-chain acylcarnitines (LCACs) which is one of the multiple factors that contribute to the ischaemia–reperfusion damage development. Long-term pre-treatment that decreases carnitine and LCAC contents also reduces ischaemia–reperfusion (IR) damage; however, the duration of the post-treatment effects is not known. The aim of the study was to assess the post-treatment effects of the carnitine transport (OCTN2) inhibitor, methyl-GBB, on LCAC content and the duration of its cardioprotective effect. Male Wistar rats received methyl-GBB (5 mg/kg for 28 days), and the anti-infarction effects on Langendorff-perfused hearts and the acylcarnitine profile in cardiac tissues were measured up to 28 days following the end of the treatment. Methyl-GBB pre-treatment for 28 days decreased LCAC heart tissue content by 87%, and the infarct size was decreased by 57%. Fourteen days post-treatment, the LCAC content was still decreased by 69%, and the infarct size was decreased by 32% compared to Control. A significant Pearson correlation (r = 0.48, p = 0.026) was found between infarct size and LCAC tissue content in the methyl-GBB-treated rat hearts. The addition of 2 mM carnitine to isolated heart perfusate significantly diminished the methyl-GBB-induced decrease in LCACs and infarct size. In conclusion, the anti-infarction effect of methyl-GBB continues for at least 2 weeks post-treatment. No less than a 70% decrease in LCAC content is required to protect ischaemic heart tissues, and the decrease in LCAC levels defines the duration of the post-treatment cardioprotective effect of the OCTN2 inhibitor, methyl-GBB.en
dc.description.statusPeer reviewed
dc.format.extent7
dc.format.extent172715
dc.identifier.citationKuka, J, Makrecka-Kuka, M, Cirule, H, Grinberga, S, Sevostjanovs, E, Dambrova, M & Liepinsh, E 2017, 'Decrease in Long-Chain Acylcarnitine Tissue Content Determines the Duration of and Correlates with the Cardioprotective Effect of Methyl-GBB', Basic and Clinical Pharmacology and Toxicology, vol. 121, no. 2, pp. 106-112. https://doi.org/10.1111/bcpt.12775
dc.identifier.doi10.1111/bcpt.12775
dc.identifier.issn1742-7835
dc.identifier.urihttps://dspace.rsu.lv/jspui/handle/123456789/4161
dc.identifier.urlhttp://www.scopus.com/inward/record.url?scp=85018337707&partnerID=8YFLogxK
dc.language.isoeng
dc.relation.ispartofBasic and Clinical Pharmacology and Toxicology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subject3.1 Basic medicine
dc.subject1.1. Scientific article indexed in Web of Science and/or Scopus database
dc.subjectToxicology
dc.subjectPharmacology
dc.titleDecrease in Long-Chain Acylcarnitine Tissue Content Determines the Duration of and Correlates with the Cardioprotective Effect of Methyl-GBBen
dc.type/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article

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