Journal
PHARMACOLOGICAL RESEARCH
Volume 85, Issue -, Pages 33-38Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2014.05.002
Keywords
Biosynthesis; Cardioprotection; Drug delivery; Reabsorbtion in kidneys; Transport
Categories
Funding
- ERDF [2DP/2.1.1.1.0/10/APIA/VIAA/063]
- Latvian National Research Program BIOMEDICINE
Ask authors/readers for more resources
L-Carnitine is a cofactor in the energy metabolism pathways where it drives the uptake and oxidation of long chain fatty acids (LCFA) by mitochondria. LCFA lipotoxicity causes mitochondrial damage and results in an insufficient energy supply and a decrease in L-carnitine content limits LCFA flux and protects mitochondria. Here, we tested whether the inhibition of GBB dioxygenase (BBOX) or organic cation transporter 2 (OCTN2) is the most effective strategy to decrease L-carnitine content. The activity of 51 compounds was tested and we identified selective inhibitors of OCTN2. In contrast to selective inhibitors of BBOX, OCTN2 inhibitors induced a 10-fold decrease in L-carnitine content in the heart tissues and a significant 35% reduction of myocardial infarct size. In addition, OCTN2 inhibition correlated with the inhibitor content in the heart tissues, and OCTN2 could potentially be an efficient target to increase drug transport into tissues and to reduce drug elimination by urine. In conclusion, the results of this study confirm that selective inhibition of OCTN2, compared to selective inhibition of BBOX, is a far more effective approach to decrease L-carnitine content and to induce cardioprotective effects. OCTN2 could potentially be an efficient tool to increase drug transport in tissues and to reduce drug elimination via urine. (C) 2014 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available