Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases.
It has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and antimitochondrial activity, including cytochrome-P450 reductase and 5 alpha-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine-xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O2- and OH. generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation.
Akamatsu
H
H
Department of Dermatology, Kansai Medical University.
Komura
J
J
Asada
Y
Y
Miyachi
Y
Y
Niwa
Y
Y
D002633:Chemotaxis / Q000187:drug effects; D003879:Dermatologic Agents / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D003998:Dicarboxylic Acids / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D006801:Humans; D006878:Hydroxides / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010087:Oxides / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D012871:Skin Diseases / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014969:Xanthine Oxidase / Q000378:metabolism
D003879:Dermatologic Agents; D003998:Dicarboxylic Acids; D006878:Hydroxides; D010087:Oxides; D014969:Xanthine Oxidase; C010038:azelaic acid