Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection

• Published in: Journal of the American College of Cardiology 2008-09, Vol.52 (13), p.1086-1094
• Main Authors: Romero-Perez, Diego, BS, Fricovsky, Eduardo, PharmD, Yamasaki, Katrina Go, BS, Griffin, Michael, PhD, Barraza-Hidalgo, Maraliz, BS, Dillmann, Wolfgang, MD, Villarreal, Francisco, MD, PhD
• Format: Article
• Language: English
• Subjects: Acids; Animals; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacokinetics; Antioxidants - therapeutic use; Biological and medical sciences; Cardiology; Cardiology. Vascular system; cardioprotection; Cardiotonic Agents - metabolism; Cardiotonic Agents - pharmacokinetics; Cardiotonic Agents - therapeutic use; Cardiovascular; Cardiovascular disease; Drug dosages; Internal Medicine; Ischemia; Laboratory animals; Male; Matrix Metalloproteinase Inhibitors; Medical sciences; Minocycline - metabolism; Minocycline - pharmacokinetics; Minocycline - therapeutic use; myocardial infarction; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Ostomy; Oxidative stress; Pharmacology. Drug treatments; pleiotropic action; Rats; Rats, Sprague-Dawley; Rodents; Studies; Up-Regulation; Veins & arteries
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2008.06.028

Cardiac Uptake of Minocycline and Mechanisms for In Vivo Cardioprotection Diego Romero-Perez, Eduardo Fricovsky, Katrina Go Yamasaki, Michael Griffin, Maraliz Barraza-Hidalgo, Wolfgang Dillmann, Francisco Villarreal Tetracyclines are being examined for their potential to prevent and/or limit the progression of many diseases. Here, we demonstrate that minocycline significantly reduces infarct size in rats subjected to ischemia-reperfusion injury. A substantial accumulation of the drug in normal and ischemic tissues was observed. The accumulation followed the capacity of cardiac cells to uptake the compound. Infarcted myocardium demonstrated reduced levels of matrix metalloproteinase-9 activity and tissue oxidative stress in animals treated with minocycline. On the basis of the millimolar concentrations observed inside the cells, it is likely that tetracyclines yield tissue protection via mass action effects.