Cardiac uptake of minocycline and mechanisms for in vivo cardioprotection.
ABSTRACT The ability of minocycline to be transported into cardiac cells, concentrate in normal and ischemic myocardium, and act as a cardioprotector in vivo was examined. We also determined minocycline's capacity to act as a reducer of myocardial oxidative stress and matrix metalloproteinase (MMP) activity.
The identification of compounds with the potential to reduce myocardial ischemic injury is of great interest. Tetracyclines are antibiotics with pleiotropic cytoprotective properties that accumulate in normal and diseased tissues. Minocycline is highly lipophilic and has shown promise as a possible cardioprotector. However, minocycline's potential as an in vivo cardioprotector as well as the means by which this action is attained are not well understood.
Rats were subjected to 45 min of ischemia and 48 h of reperfusion. Animals were treated 48 h before and 48 h after thoracotomy with either vehicle or 50 mg/kg/day minocycline. Tissue samples were used for biochemical assays and cultured cardiac cells for minocycline uptake experiments.
Minocycline significantly reduced infarct size (approximately 33%), tissue MMP-9 activity, and oxidative stress. Minocycline was concentrated approximately 24-fold in normal (0.5 mmol/l) and approximately 50-fold in ischemic regions (1.1 mmol/l) versus blood. Neonatal rat cardiac fibroblasts, myocytes, and adult fibroblasts demonstrated a time- and temperature-dependent uptake of minocycline to levels that approximate those of normal myocardium.
Given the high intracellular levels observed and results from the assessment of in vitro antioxidant and MMP inhibitor capacities, it is likely that minocycline acts to limit myocardial ischemic injury via mass action effects.
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ABSTRACT: The capacity of minocycline to alleviate disease for several neurological disorders in animals is increasingly being recognised. Indeed, that one drug alone can attenuate the severity of disease in stroke, multiple sclerosis, spinal-cord injury, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis is astounding. In this review, we describe the evidence for the efficacy of minocycline in several animal models of neurological disease, discuss the mechanisms by which minocycline affects a range of neurological diseases with diverse causes, and introduce the emerging investigation of minocycline in clinical neurology. The encouraging results of minocycline in experimental neurology bode well for its therapeutic use in human neurological diseases.The Lancet Neurology 01/2005; 3(12):744-51. · 23.46 Impact Factor
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ABSTRACT: Tetracyclines (TCN) were introduced in 1948 as broad-spectrum antibiotics that may be used in the treatment of many common infections in children and adults. One of the side-effects of tetracyclines is incorporation into tissues that are calcifying at the time of their administration. They have the ability to chelate calcium ions and to be incorporated into teeth, cartilage and bone, resulting in discoloration of both the primary and permanent dentitions. This permanent discoloration varies from yellow or gray to brown depending on the dose or the type of the drug received in relation to body weight. Minocycline hydrochloride, a semisynthetic derivative of tetracycline often used for the treatment of acne, has been shown to cause pigmentation of a variety of tissues including skin, thyroid, nails, sclera, teeth, conjunctiva and bone. Adult-onset tooth discoloration following long-term ingestion of tetracycline and minocycline has also been reported. The remarkable side-effect of minocycline on the oral cavity is the singular occurrence of "black bones", "black or green roots" and blue-gray to gray hue darkening of the crowns of permanent teeth. The prevalence of tetracycline and minocycline staining is 3-6%. The mechanism of minocycline staining is still unknown. Most of the reviewed literature consisted of case reports; longitudinal clinical trials are necessary to provide more information on the prevalence, severity, etiology and clinical presentation of tetracycline and TCN-derivative staining in the adult population.International Journal of Dermatology 11/2004; 43(10):709-15. · 1.14 Impact Factor