0000000000396997
AUTHOR
Maria S. Santos
Targeting the Mitochondria by Novel Adamantane-Containing 1,4-Dihydropyridine Compounds
Linda Klimaviciusa1, Maria A. S. Fernandes2, Nelda Lencberga1, Marta Pavasare1, Joaquim A. F. Vicente2, Antonio J. M. Moreno2, Maria S. Santos3, Catarina R. Oliveira4, Imanta Bruvere5, Egils Bisenieks5, Brigita Vigante5 and Vija Klusa1 1Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga 2IMAR-CMA, Department of Life Sciences, University of Coimbra, Coimbra 3CNC, Department of Life Sciences, University of Coimbra, Coimbra 4CNC, Faculty of Medicine, University of Coimbra, Coimbra 5Laboratory of Membrane Active and beta-Diketone Compounds, Latvian Institute of Organic Synthesis, Riga 2,3,4Portugal 1,5Latvia
Mitochondria as the target for mildronate's protective effects in azidothymidine (AZT)-induced toxicity of isolated rat liver mitochondria
Previously mildronate, an aza-butyrobetaine derivative, was shown to be a cytoprotective drug, through its mechanism of action of inhibition of carnitine palmitoyltransferase-1, thus protecting mitochondria from long-chain fatty acid accumulation and subsequent damage. Recently in an azidothymidine (AZT)-induced cardiotoxicity model in vivo (in mice), we have found mildronate's ability of protecting heart tissue from nuclear factor kappaB abnormal expression. Preliminary data also demonstrate cerebro- and hepatoprotecting properties of mildronate in AZT-toxicity models. We suggest that mildronate may target its action predominantly to mitochondria. The present study in isolated rat liver mi…