Anti-inflammatory action of gentamycin through inhibitory effect on neutrophil NADPH oxidase activity.
The effects of gentamycin on the NADPH oxidase (EC 1.6.99.6) from human neutrophils in both whole-cell and fully soluble (cell-free) systems were investigated. Gentamycin was found to inhibit, concentration-dependently, the superoxide generation of neutrophils exposed to phorbol myristate acetate in a whole-cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. The concentrations of the drug required for 50% inhibition of the oxidase (IC50) were 150 microM in the whole-cell system and 10 microM in the cell-free system. In addition, in the cell-free system, the drug did not change the Km value for NADPH of the oxidase. However, gentamycin did not the superoxide generation of NADPH oxidase after its activation in the cell-free system, suggesting that the drug do not have superoxide-scavenger action. These results suggest that gentamycin, an aminoglycoside antibiotic, may exhibit an anti-inflammatory action due to inhibition of neutrophil NADPH oxidase activation.
Umeki
S
S
Department of Medicine, Toshida-Kai Kumeda Hospital, Osaka, Japan.
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002474:Cell-Free System; D004789:Enzyme Activation / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D009247:NADH, NADPH Oxidoreductases / Q000097:blood / Q000187:drug effects*; D019255:NADPH Oxidases; D009504:Neutrophils / Q000201:enzymology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005839:Gentamicins; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases