Effects of long-term mildronate treatment on cardiac and liver functions in rats

Edgars Liepinsh, Janis Kuka, Baiba Svalbe, Reinis Vilskersts, Elina Skapare, Helena Cirule, Osvalds Pugovics, Ivars Kalvinsh, Maija Dambrova

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Mildronate is a cardioprotective drug that improves cardiac function during ischaemia and functions by lowering l-carnitine concentration in body tissues and modulating myocardial energy metabolism. The aim of the present study was to characterise cardiovascular function and liver condition after long-term mildronate treatment in rats. In addition, changes in the plasma lipid profile, along with changes in the concentration of mildronate, l-carnitine and γ-butyrobetaine were monitored in the rat tissues. Wistar rats were perorally treated daily with a mildronate dose of either 100, 200 or 400 mg/kg for 4, 8 or 12 weeks. The l-carnitine-lowering effect of mildronate was dose-dependent. However, the carnitine levels reached a plateau after about four weeks of treatment. During the additional weeks of treatment, the carnitine levels were not considerably changed. The obtained results provide evidence that even a high dose of mildronate does not alter cardiovascular parameters and the function of isolated rat hearts. Furthermore, the histological evaluation of liver tissue cryosections and measurement of biochemical markers of hepatic toxicity showed that all the measured values were within the normal reference range. Our results provide evidence that long-term mildronate administration induces significant changes in carnitine homeostasis, but it is not associated with cardiac impairment or disturbances in liver function.

Original languageEnglish
Pages (from-to)387-394
Number of pages8
JournalBasic and Clinical Pharmacology and Toxicology
Volume105
Issue number6
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

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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