Potentiation of the generation of reactive oxidants by human phagocytes during exposure to benoxaprofen and ultraviolet radiation in vitro.
The effects of ultraviolet (UV) radiation on the spontaneous membrane-associated oxidative metabolism of human polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (MNL), co-incubated in the presence and absence of the non-steroidal, anti-inflammatory drug (NSAID) benoxaprofen at various concentrations, were investigated in vitro. Assays of superoxide generation and luminol-enhanced chemiluminescence (CL) were used to detect the production of reactive oxidants by PMNL and MNL. Benoxaprofen in the absence of UV radiation caused a dose-related activation of superoxide production and CL by PMNL. Exposure of PMNL to UV radiation in the absence of benoxaprofen caused a slight increase in superoxide generation and an unsustained slight increase in CL within 10 s. Exposure of both MNL and PMNL to UV radiation in the presence of benoxaprofen had a marked synergistic effect on both superoxide generation and CL. These effects were also achieved with UVA irradiation but were not detected when adherent cell depleted MNL or sodium fluoride (NaF) (10-2 M) pulsed PMNL, or PMNL from children with chronic granulomatous disease, were used. The pro-oxidative effects of benoxaprofen and UV radiation alone and in combination are dependent on intact phagocyte membrane-associated oxidative metabolism. It is postulated that the pro-oxidative interactions which occur between human phagocytes, benoxaprofen and ultraviolet radiation cause the dermatological side-effects of benoxaprofen.
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002648:Child; D006105:Granulomatous Disease, Chronic / Q000097:blood; D006801:Humans; D008163:Luminescent Measurements; D009504:Neutrophils / Q000378:metabolism; D010083:Oxidants, Photochemical / Q000378:metabolism*; D010586:Phagocytes / Q000187:drug effects* / Q000528:radiation effects; D011422:Propionates / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; D010083:Oxidants, Photochemical; D011422:Propionates; D013481:Superoxides; C011677:benoxaprofen