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

Janis Kuka, Marina Makrecka-Kuka, Helena Cirule, Solveiga Grinberga, Eduards Sevostjanovs, Maija Dambrova, Edgars Liepinsh

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Ischaemia 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.

Original languageEnglish
Pages (from-to)106-112
Number of pages7
JournalBasic and Clinical Pharmacology and Toxicology
Volume121
Issue number2
DOIs
Publication statusPublished - Aug 2017

Field of Science

  • 3.1 Basic medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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