Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity.
Minocycline is neuroprotective in animal models of a number of acute CNS injuries and neurodegenerative diseases. While anti-inflammatory and anti-apoptotic effects of minocycline have been characterized, the molecular basis for the neuroprotective effects of minocycline remains unclear. We report here that minocycline and a number of antioxidant compounds protect mixed neuronal cultures in an oxidative stress assay. To evaluate the role of minocycline's direct antioxidant properties in neuroprotection, we determined potencies for minocycline, other tetracycline antibiotics, and reference antioxidant compounds using a panel of in vitro radical scavenging assays. Data from in vitro rat brain homogenate lipid peroxidation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays show that minocycline, in contrast to tetracycline, is an effective antioxidant with radical scavenging potency similar to vitamin E. Our findings suggest that the direct antioxidant activity of minocycline may contribute to its neuroprotective effects in some cell-based assays and animal models of neuronal injury.
Kraus
Richard L
RL
Department of Molecular Neuroscience, Merck Research Laboratories San Diego, California 92121, USA.
Pasieczny
Rodger
R
Lariosa-Willingham
Karen
K
Turner
Mary S
MS
Jiang
Alice
A
Trauger
John W
JW
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D052160:Benzothiazoles; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002839:Chromans / Q000494:pharmacology; D003855:Deoxyribose / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000077553:Edaravone; D004622:Embryo, Mammalian; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008911:Minocycline / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010627:Phenethylamines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013451:Sulfonic Acids / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D052160:Benzothiazoles; D002839:Chromans; D016166:Free Radical Scavengers; D005609:Free Radicals; D018696:Neuroprotective Agents; D010627:Phenethylamines; D013451:Sulfonic Acids; C057485:1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane; D014810:Vitamin E; C002502:2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid; D018698:Glutamic Acid; D003855:Deoxyribose; D016291:Dizocilpine Maleate; D007770:L-Lactate Dehydrogenase; D008911:Minocycline; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D000077553:Edaravone; D000983:Antipyrine