ABSTRACT
Apocynin, a methoxy-substituted catechol (4-hydroxy-3-methoxyacetophenone), originally extracted from the roots of Picrorhiza kurroa, has been extensively used as a non-toxic inhibitor of the multienzymatic complex NADPH oxidase. We discovered that the analogous methoxy-substituted catechol, 4-Fluoro-2-methoxyphenol (F-apocynin), in which the acetyl group present in apocynin was changed to a fluorine atom, was significantly more potent as an inhibitor of NADPH oxidase activity, myeloperoxidase (MPO) chlorinating activity and phagocytosis of microorganisms by neutrophils; it was also as potent as apocynin in inhibiting tumor necrosis factor-alpha (TNFα) release by peripheral blood mononuclear cells. We attribute the increased potency of F-apocynin to its increased lipophilicity, which could facilitate the passage of the drug through the cell membrane. The inhibition of MPO chlorination activity, phagocytosis and TNFα release shows that apocynin and F-apocynin actions are not restricted to reactive oxygen species inhibition, but further studies are needed to clarify if these mechanisms are related. Like apocynin, F-apocynin did not show cell toxicity, and is a strong candidate for use in the treatment of inflammatory diseases.
Subject(s)
Acetophenones/chemistry , Guaiacol/analogs & derivatives , Leukocytes/drug effects , Oxidants/biosynthesis , Phagocytosis/drug effects , Acetophenones/metabolism , Acetophenones/pharmacology , Acetophenones/toxicity , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Candida albicans/physiology , Cell Membrane/drug effects , Cell Membrane/metabolism , Guaiacol/chemistry , Guaiacol/metabolism , Guaiacol/pharmacology , Guaiacol/toxicity , Humans , Hydrophobic and Hydrophilic Interactions , Hypochlorous Acid/metabolism , Leukocytes/immunology , Leukocytes/metabolism , Leukocytes/microbiology , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Neutrophils/drug effects , Neutrophils/metabolism , Peroxidase/metabolism , Reactive Oxygen Species/metabolism , Staphylococcus aureus/physiology , Superoxides/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Presentamos el caso de una mujer joven que sufrió intoxicación por guayacol (metoxifenol), cuyo desenlace fue fatal. Presentó alteraciones neurológicas, hemodinámicas (choque), respiratorias (hipoxemia refractaria), metabólicas (acidosis metabólica grave), renales (necrosis tubular aguda), digestivas y hematológicas. Motivo de defunción: Edema agudo pulmonar grave secundario a congestión visceral generalizadas. Todas las alteraciones antes mencionadas correlacionaron con lo evidenciado en los exámenes de laboratorio, electrocardiograma y necropsia. Tal vez este sea el primer caso de intoxicación por guayacol (metoxifenol) registrado en el mundo