The priming effect of gemfibrozil on reactive oxygen metabolism of phagocytic leucocytes. An intriguing side effect.
Gemfibrozil is an antihyperlipidaemia agent used in therapy to reduce the occurrence of coronary heart disease. Considering the biochemical and pharmacological peculiarities of this class of drugs, we investigated the influence of a single oral therapeutic dose of gemfibrozil on the reactive oxygen metabolism of phagocytic leucocytes. Analysis was carried out adopting a chemiluminescence assay. Results clearly indicate that gemfibrozil, acting as a primer, significantly enhances the induced reactive-oxygen-species (ROS) production by overall blood phagocytes (increment of Stimulation Index (SI) = +52% with respect to time 0 values; P < 0.01), by polymorphonuclear leucocytes (increment of SI = +28% with respect to control values; P < 0.01) and by monocytes (increment of SI = +83% with respect control values; P < 0.001), when these cells are stimulated by phorbol myristate acetate. This iatrogenic derangement of ROS metabolism could explain, at least in part, the occurrence of some side effects that occur in treatment with fibrates.
Scatena
R
R
Institute of Chemistry and Clinical Chemistry, Faculty of Medicine, Catholic University, Rome, Italy.
Nocca
G
G
De Sole
P
P
Fresu
R
R
Zuppi
C
C
Giardina
B
B
D000328:Adult; D015248:Gemfibrozil / Q000494:pharmacology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010586:Phagocytes / Q000187:drug effects* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000960:Hypolipidemic Agents; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate; D015248:Gemfibrozil