Inhibition of human neutrophil oxidative burst by pyrazolone derivatives.
The risk of agranulocytosis associated with the use of pyrazolone drugs at therapeutical doses and for short periods of time has been considered to be very low. However, little or no attention at all has been devoted to the possible hindrance of neutrophil burst and scavenging of neutrophil-generated reactive oxygen species (ROS) by these compounds. Such an effect could be beneficial in the case of overactivation of neutrophils but could also be highly detrimental if the number of circulating neutrophils is already decreased. Thus, the aim of the present study was to evaluate the putative inhibitory effect of the pyrazolones dipyrone, aminopyrine, isopropylantipyrine, and antipyrine against human neutrophil burst and their scavenging activity against O2.-, H2O2, HO., ROO., and HOCl. The obtained results showed that dipyrone and aminopyrine prevent phorbol-12-myristate-13-acetate-induced neutrophil burst with high efficiency, while isopropylantipyrine had little effect and antipyrine had no effect at all. Dipyrone and aminopyrine were highly potent scavengers of HO. and HOCl, while, in accordance with the neutrophil burst results, isopropylantipyrine had little effect and antipyrine had no effect at all against these two ROS. None of the studied pyrazolones was capable of scavenging O2.- or H2O2, while dipyrone was shown to be the most reactive against ROO..
Costa
David
D
REQUIMTE, Departamento de Química-Física, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha, 164, 4099-030 Porto, Portugal.
Marques
Alexandra P
AP
Reis
Rui L
RL
Lima
José L F C
JL
Fernandes
Eduarda
E
D000632:Aminopyrine / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D004177:Dipyrone / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D047069:Pyrazolones / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016166:Free Radical Scavengers; D047069:Pyrazolones; D017382:Reactive Oxygen Species; D000632:Aminopyrine; C038362:pyrazolone; D004177:Dipyrone; D013755:Tetradecanoylphorbol Acetate; C009077:propyphenazone; D000983:Antipyrine