Summary
Metronidazole is clinically effective in treating not only rosacea but also acne inflammation. Yet it is generally considered not to be very effective in inhibiting the growth of anaerobic Propionibacterium acnes. We report here our investigation into the synergistic effects of metronidazole and palmitoleic acid on the anaerobic growth of P. acnes as well as on human neutrophil functions, including the generation of reactive oxygen species (ROS). Both metronidazole and palmitoleic acid, when used alone, only slightly inhibited the growth of P. acnes, and no significant decrease in human neutrophil functions, including the generation of ROS, was observed. But metronidazole used in the presence of palmitoleic acid markedly inhibited the anaerobic growth of P. acnes and decreased ROS generation by neutrophils. However, ROS generated in the xanthine-xanthine oxidase system were not affected. Metronidazole was shown to be clinically effective by decreasing neutrophil-generated ROS at the sites of inflammation with the aid of palmitoleic acid, which is generally present in human skin. By inhibiting oxidative tissue injury under in vivo conditions, treatment with metronidazole results in remarkable improvement of rosacea and acne.
Similar content being viewed by others
References
Akamatsu H, Oguchi M, Asada M, Kubo K, Namura S, Shirai K, Nishijima S. Asada Y (1987) Treatment of acne with oral metronidazole. Proceedings of the 5th Korea-Japan Joint Meeting of Dermatology, 6–7 Nov, Cheju, Korea; pp 137–140
Bingham R (1985) Anti-malarial and anti-protozoal drugs in the treatment of rheumatoid diseases. A preliminary report. 16th International Congress of Rheumatology, Sydney, Australia Excerpta Medica, Elsevier Science Publishers. BV, Amsterdam, p 22
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917
Ely PH (1985) Flagyl: beneficial in psoriasis? Schoch Lett 35:9–13
Goto S, Kawakita T, Kozaki N, Mitsuhashi S, Nishino T, Osawa N, Tanami H (1981) Methods for determination of minimum inhibitory concentration (MIC). Chemotherapy 29:76–79
Johnson AR, Erdos G (1977) Metabolism of vasoactive peptides by human endothelial cells in culture. J Clin Invest 59:684–695
Johnston RB Jr, Lehmeyer JE (1976) Elaboration of toxic oxygen by-products by neutrophils and a model of immune complex disease. J Clin Invest 57:836–841
Klebanoff SJ, Rosen H (1978) Ethylene formation by polymorphonuclear leukocytes. J Exp Med 148:490–505
Kosakai N, Ueno K, Goto S, Mihashi S, Nakayama K, Shimada K, Tamai K, Oguri T (1972) Agar dilution procedure for antimicrobial susceptibility testing of anaerobic bacteria. Chemotherapy 27:559–561
Massey V (1959) The microestimation of succinate and the extinction coefficient of cytochrome c. Biochim Biophys Acta 34:255–256
Miyachi Y, Niwa Y (1983) Effects of psoriatic sera on the generation of oxygen intermediates by normal polymorphonuclear leukocytes. Arch Dermatol Res 275:23–26
Miyachi Y, Imamura S, Niwa Y (1986) Anti-oxidant action of metronidazole: a possible mechanism of action in rosacea. Br J Dermatol 114:231–234
Miyachi Y, Yoshioka A, Imamura S, Niwa Y (1986) Effect of antibiotics on the generation of reactive oxygen species. J Invest Dermatol 86:449–453
Miyachi Y, Yoshioka A, Imamura S, Niwa Y (1987) Antiinflammatory activities of tetracyclines are partly exerted by their anti-oxidant effect. Proceedings of the 4th International Congress of Pediatric Dermatology. Urabe H, Kimura M, Yamamoto K, Ogawa H (eds) University of Tokyo Press, Tokyo, pp 291–294
Nelson RD, Quie PG, Simmons RL (1977) Chemotaxis under agarose. A new and simple method for measuring chemotaxis and spontaneous migration of human polymorphonuclear leukocytes and monocytes. J Immunol 115:1650–1656
Niwa Y, Sakane T, Shingu M, Yokoyama MM (1983) Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes — a possible role of increased oxygen radicals generated by the neutrophils. J Clin Immunol 3:228–240
Niwa Y, Sakane T, Shingu M, Yanagida I, Komura J, Miyachi Y (1985) Neutrophil-generated active oxygens in linear IgA bullous dermatosis. Arch Dermatol 121:73–78
Niwa Y, Kasama T, Miyachi Y, Kanoh T (1989) Neutrophil chemotaxis, phagocytosis and parameters of reactive oygen species in human aging: cross-sectional and longitudinal studies. Life Sci 44:1655–1664
Puhvel SM, Sakamoto M (1977) A re-evaluation of fatty acids as inflammatory agents in acne. J Invest Dermatol 68:93–99
Pye RJ, Burton JL (1976) Treatment of rosacea by metronidazole. Lancet I:1211–1215
Root RK, Metcalf JA (1972) H2O2 release from human granulocytes during phagocytosis. J Clin Invest 60:1266–1279
Saihan EM, Burton JL (1980) A double-blind trial of metronidazole versus oxytetracycline therapy for rosacea. Br J Dermatol 102:443–448
Skosey JL, Damgaard E, Chow DC, Sorensen LB (1974) Modification of zymosan-induced release of lysosomal enzymes from polymorphonuclear leukocytes by cytochalasin B. J Cell Biol 62:625–634
Stossel TP (1973) Evaluation of opsonic and leukocyte function with a spectrophotometric test in patients with infection and with phagocytic disorders. Blood 42:121–130
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Akamatsu, H., Oguchi, M., Nishijima, S. et al. The inhibition of free radical generation by human neutrophils through the synergistic effects of metronidazole with palmitoleic acid: a possible mechanism of action of metronidazole in rosacea and acne. Arch Dermatol Res 282, 449–454 (1990). https://doi.org/10.1007/BF00402621
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00402621