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.
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.
Akamatsu
H
H
Department of Dermatology, Kansai Medical University, Moriguchi, Japan.
Oguchi
M
M
Nishijima
S
S
Asada
Y
Y
Takahashi
M
M
Ushijima
T
T
Niwa
Y
Y
D000152:Acne Vulgaris / Q000188:drug therapy / Q000378:metabolism; D004357:Drug Synergism; D005229:Fatty Acids, Monounsaturated; D005609:Free Radicals; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008795:Metronidazole / Q000494:pharmacology* / Q000627:therapeutic use; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D010169:Palmitic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011425:Propionibacterium acnes / Q000187:drug effects / Q000502:physiology; D012393:Rosacea / Q000188:drug therapy / Q000378:metabolism
D005229:Fatty Acids, Monounsaturated; D005609:Free Radicals; D010169:Palmitic Acids; D008795:Metronidazole; C008757:palmitoleic acid; D010100:Oxygen