Prevention of peroxidase mediated inhibition of neutrophil motility and lymphocyte transformation by levamisole, OMPI, sodium aurothiomalate, indomethacin and tolmetin in vitro

Oosthuizen, R; Grabow, G

doi:10.1016/0192-0561(81)90002-3

Cited by 10 publications

(2 citation statements)

References 19 publications

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“…Interaction of benoxaprofen with PMNL causes enhanced oxidative metabolism and extracellular release of myeloperoxidase. The extracellular activity of the MPO/H202/halide system has been reported to promote the auto-oxidative inhibition of PMNL migration [16]. Activation of this system by benoxaprofen could explain the observed inhibition of PMNL migration and the protective effects of the water soluble anti-oxidants, ascorbate and levamisole.…”

Section: Tablementioning

confidence: 96%

Benoxaprofen: A pro-oxidant anti-inflammatory drug?

1984

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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 greater than 1 X 10(-6) M and 1 X 10(-5) M respectively. Benoxaprofen per 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-iodination. 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 functions in vitro (mean serum value 126 micrograms/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.

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Section: Tablementioning

confidence: 96%

Benoxaprofen: A pro-oxidant anti-inflammatory drug?

1984

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“…M. ieprae antigens (e) bind with antibody (y) to form localized or circulating immune complexes which are deposited in the skin,joints, kidney or endothelial cells of blood vessels. Resultant complement activation releases factors (C3a and C5a) which activate and attract phagocytes, especially PMNL and the cell membrane attack unit C5b, 6,7,8,9 (00000). These cells bind to the immune complexes but are unable to ingest them (since the complexes are tissue bound).…”

mentioning

confidence: 99%

The immunopharmacology of antileprosy agents

ANDERSON

1983

Leprosy Review

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Novel assay and pharmacokinetics of levamisole and p‐hydroxylevamisole in human plasma and urine

Kouassi

Caillé

Léry

et al. 1986

Biopharm & Drug Disp

104

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A new gas chromatographic method was developed for the quantification of levamisole in human plasma and urine, using a nitrogen-phosphorus flame ionization detector. The adsorption of the drug onto glass was prevented by treating the glassware with a siliconizing agent. The sensitivity of the assay was 10 ng ml-1 and as low as 2 ng ml-1 can be detected in plasma. The urinary metabolite p-hydroxylevamisole was analysed by high performance liquid chromatography with ultraviolet detection. The sensitivity of this assay was 0.50 micrograms ml-1. Plasma and urinary concentrations of levamisole were determined in 10 healthy volunteers including seven men and three women following the administration of a single 150 mg dose of levamisole. Levamisole was rapidly absorbed (tmax 1.5 h), giving a peak plasma concentration of 716.7 +/- 217.5 ng ml-1. The plasma elimination half-life of levamisole was 5.6 +/- 2.5 h. Only 3.2 +/- 2.9 per cent of the oral dose was recovered as unchanged drug in the urine, suggesting the importance of clearance of levamisole by routes other than the kidney, and most probably by hepatic metabolism. The urinary concentrations of p-hydroxylevamisole were determined before and after hydrolysis of the urine samples with beta-glucuronidase, and the level of conjugation of the metabolite with glucuronic acid was then estimated. Cumulative recovery of the metabolite accounted for 1.6 +/- 1.1 per cent and 12.4 +/- 5.5 per cent of the oral dose of levamisole before and after hydrolysis, respectively, indicating that p-hydroxylation is a relatively important route of metabolism of levamisole, and that the p-hydroxylated metabolite is excreted mainly in conjugation with glucuronic acid. Except for the absorption rate of levamisole which is approximately twice as rapid in women as in men, there is no marked difference in the pharmacokinetics of levamisole between healthy men and women.

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Prevention of peroxidase mediated inhibition of neutrophil motility and lymphocyte transformation by levamisole, OMPI, sodium aurothiomalate, indomethacin and tolmetin in vitro

Cited by 10 publications

References 19 publications

Benoxaprofen: A pro-oxidant anti-inflammatory drug?

Benoxaprofen: A pro-oxidant anti-inflammatory drug?

The immunopharmacology of antileprosy agents

Novel assay and pharmacokinetics of levamisole and p‐hydroxylevamisole in human plasma and urine

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