ISSN:
1420-908X
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Benoxaprofen inhibited the random motility and migration to the leucoattractants endotoxin-activated serum (EAS) and f-met-leu-phe of human polymorphonuclear leucocytes (PMNL)in vitro. Inhibition of random and leucoattractant-induced migration was observed at drug concentrations of 〉1×110−6 M and 1×10−5 M respectively. Benoxaprofenper se was not leucotactic but was pro-oxidative in that it stimulated PMNL hexose-monophosphate shunt activity, chemiluminescence, myeloperoxidase-mediated iodination reactions and degranulation. The drug also mediated auto-oxidation of PMNL as measured by cellular auto-lodination. The relationship between benoxaprofen-mediated inhibition of PMNL migration and activation of oxidative metabolism was investigated using the anti-oxidants ascorbate and levamisole at concentrations of 10−2 M and 10−3 M respectively. These agents prevented the decreased motility and auto-oxidation of PMNL induced by 10−4 M benoxaprofen. Benoxaprofen (10−4 M) did not inhibit the migration of PMNL from 3 children with chronic granulomatous disease thus showing that intact PMNL oxidative metabolism is required for the induction of drug-mediated inhibition of cell motility. Ingestion of therapeutic doses of benoxaprofen for 7 days by normal adults gave serum drug concentrations greater than those required for detectable effects on PMNL functionsin vitro (mean serum value 126 μg/ml). Co-incubation of normal PMNL with serum from individuals who had ingested the drug caused decreased cell migration and increased chemiluminescence. These results show that benoxaprofen inhibits PMNL migration as a consequence of pro-oxidant properties and despite its withdrawal may be the prototype of the pro-oxidative anti-inflammatory drug.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01966648
