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 anti-mitochondrial activity, including cytochrome-P₄₅₀ reductase and 5α-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.