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Publikācija: Mildronate

Publication Type Scientific article indexed in SCOPUS or WOS database
Funding for basic activity Unknown
Defending: ,
Publication language English (en)
Title in original language Mildronate, an Inhibitor of Carnitine Biosynthesis, Induces an Increase in Gamma-Butyrobetaine Contents and Cardioprotection in Isolated Rat Heart Infarction
Field of research 3. Medical and Health sciences
Sub-field of research 3.1 Basic medicine including pharmacy
Authors Edgars Liepiņš
Reinis Vilskersts
Dagnija Loča
Olga Kirjanova
Osvalds Pugovičs
Ivars Kalviņš
Maija Dambrova
Keywords -
Abstract The inhibition of gamma-butyrobetaine (GBB) hydroxylase, a key enzyme in the biosynthesis of carnitine, contributes to lay ground for the cardioprotective mechanism of action of mildronate. By inhibiting the biosynthesis of carnitine, mildronate is supposed to induce the accumulation of GBB, a substrate of GBB hydroxylase. This study describes the changes in content of carnitine and GBB in rat plasma and heart tissues during long-term (28 days) treatment of mildronate [i.p. (intraperitoneal) 100 mg/kg/daily]. Obtained data show that in concert with a decrease in carnitine concentration, the administration of mildronate caused a significant increase in GBB concentration. We detected about a 5-fold increase in GBB contents in the plasma and brain and a 7-fold increase in the heart. In addition, we tested the cardioprotective effect of mildronate in isolated rat heart infarction model after 3, 7, and 14 days of administration.We found a statistically significant decrease in necrotic area of infarcted rat hearts after 14 days of treatment with mildronate. The cardioprotective effect of mildronate correlated with an increase in GBB contents. In conclusion, our study, for the first time, provides experimental evidence that the long-term administration of mildronate not only decreases free carnitine concentration, but also causes a significant increase in GBB concentration, which correlates with the cardioprotection of mildronate.
DOI: 10.1097/01.fjc.0000250077.07702.23
Hyperlink: http://journals.lww.com/cardiovascularpharm/Fulltext/2006/12000/Mildronate,_an_Inhibitor_of_Carnitine.8.aspx 
Reference Liepiņš, E., Vilskersts, R., Loča, D., Kirjanova, O., Pugovičs, O., Kalviņš, I., Dambrova, M. Mildronate, an Inhibitor of Carnitine Biosynthesis, Induces an Increase in Gamma-Butyrobetaine Contents and Cardioprotection in Isolated Rat Heart Infarction. Journal of Cardiovascular PharmacoIogy, 2006, Vol.48, Iss.6, pp.314-319. ISSN 0160-2446. e-ISSN 1533-4023. Available from: doi:10.1097/01.fjc.0000250077.07702.23
Additional information Citation count:
ID 7136