Effects of tenoxicam on superoxide anion formation, β-glucuronidase release and fMLP binding in human neutrophils: Comparison with other NSAIDs

S. Colli, S. Colombo, E. Tremoli, E. Stragliotto, S. Nicosia

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are considered to exert their activity by interfering with the generation of arachidonate metabolites in various cells, mainly in neutrophils and monocytes. The inhibition of cellular cyclooxygenase enzyme, however, does not always correlate with the in vivo activity of these drugs. Recent evidence indicates that several NSAIDs may interfere with the stimulus-response coupling of inflammatory cells. In this study, the effects of tenoxicam, an oxicam derivative with a thienothiazine structure, on neutrophil activation were evaluated by the assessment of the following parameters: (1) superoxide anion generation by neutrophils and whole blood stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187 and serum treated zymosan (STZ); (2) β-glucuronidase release from neutrophils stimulated with fMLP, A23187 and STZ; (3) binding of [3H]fMLP to intact neutrophils. The results were compared to those obtained using piroxicam and diclofenac. Tenoxicam, added in vitro to whole blood, at concentrations ranging between 10-5 and 3 x 10-4 m, significantly inhibited the generation of superoxide anion induced by fMLP, A23187 and STZ. The activity of tenoxicam on whole blood was similar to that of piroxicam, whereas diclofenac had only minimal effects on this experimental system. In isolated cells tenoxicam inhibited the generation of superoxide anion induced by A23187 and STZ. In addition, at the 3 x 10-4 M concentration, tenoxicam and diclofenac similarly inhibited O2 - generation by neutrophils stimulated with fMLP, whereas piroxicam only minimally affected this parameter. Tenoxicam also slightly, but not significantly, inhibited β-glucuronidase release by isolated neutrophils induced by all the agonists used. Specific binding of [3H]fMLP to neutrophils was inhibited by the three NSAIDs tested in a dose-dependent fashion and tenoxicam was the most potent. The affinities (Kd) of tenoxicam, piroxicam and diclfenac wre 1.11, 1.80 and 2.70 × 10-5 m, respectively. Te mechanism and inhibition of [3H]fMLP binding by tenoxicam was non-competitive. It is concluded that tenoxicam, at concentration achievable in plasma at steady state, effectively inhibits some of the processes involved in the neutrophil activation, which bear some relevane in the inflammatory disease.

Original languageEnglish
Pages (from-to)367-379
Number of pages13
JournalPharmacological Research
Volume23
Issue number4
DOIs
Publication statusPublished - 1991

Fingerprint

tenoxicam
methionyl-leucyl-phenylalanine
Glucuronidase
Superoxides
Neutrophils
Anti-Inflammatory Agents
Piroxicam
Zymosan
Pharmaceutical Preparations
Calcimycin
Diclofenac
Neutrophil Activation
Serum
N-Formylmethionine Leucyl-Phenylalanine
Calcium Ionophores

Keywords

  • fMLP
  • neutrophils
  • NSAIDS
  • superoxide anion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of tenoxicam on superoxide anion formation, β-glucuronidase release and fMLP binding in human neutrophils : Comparison with other NSAIDs. / Colli, S.; Colombo, S.; Tremoli, E.; Stragliotto, E.; Nicosia, S.

In: Pharmacological Research, Vol. 23, No. 4, 1991, p. 367-379.

Research output: Contribution to journalArticle

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abstract = "Non-steroidal anti-inflammatory drugs (NSAIDs) are considered to exert their activity by interfering with the generation of arachidonate metabolites in various cells, mainly in neutrophils and monocytes. The inhibition of cellular cyclooxygenase enzyme, however, does not always correlate with the in vivo activity of these drugs. Recent evidence indicates that several NSAIDs may interfere with the stimulus-response coupling of inflammatory cells. In this study, the effects of tenoxicam, an oxicam derivative with a thienothiazine structure, on neutrophil activation were evaluated by the assessment of the following parameters: (1) superoxide anion generation by neutrophils and whole blood stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187 and serum treated zymosan (STZ); (2) β-glucuronidase release from neutrophils stimulated with fMLP, A23187 and STZ; (3) binding of [3H]fMLP to intact neutrophils. The results were compared to those obtained using piroxicam and diclofenac. Tenoxicam, added in vitro to whole blood, at concentrations ranging between 10-5 and 3 x 10-4 m, significantly inhibited the generation of superoxide anion induced by fMLP, A23187 and STZ. The activity of tenoxicam on whole blood was similar to that of piroxicam, whereas diclofenac had only minimal effects on this experimental system. In isolated cells tenoxicam inhibited the generation of superoxide anion induced by A23187 and STZ. In addition, at the 3 x 10-4 M concentration, tenoxicam and diclofenac similarly inhibited O2 - generation by neutrophils stimulated with fMLP, whereas piroxicam only minimally affected this parameter. Tenoxicam also slightly, but not significantly, inhibited β-glucuronidase release by isolated neutrophils induced by all the agonists used. Specific binding of [3H]fMLP to neutrophils was inhibited by the three NSAIDs tested in a dose-dependent fashion and tenoxicam was the most potent. The affinities (Kd) of tenoxicam, piroxicam and diclfenac wre 1.11, 1.80 and 2.70 × 10-5 m, respectively. Te mechanism and inhibition of [3H]fMLP binding by tenoxicam was non-competitive. It is concluded that tenoxicam, at concentration achievable in plasma at steady state, effectively inhibits some of the processes involved in the neutrophil activation, which bear some relevane in the inflammatory disease.",
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T1 - Effects of tenoxicam on superoxide anion formation, β-glucuronidase release and fMLP binding in human neutrophils

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AU - Stragliotto, E.

AU - Nicosia, S.

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N2 - Non-steroidal anti-inflammatory drugs (NSAIDs) are considered to exert their activity by interfering with the generation of arachidonate metabolites in various cells, mainly in neutrophils and monocytes. The inhibition of cellular cyclooxygenase enzyme, however, does not always correlate with the in vivo activity of these drugs. Recent evidence indicates that several NSAIDs may interfere with the stimulus-response coupling of inflammatory cells. In this study, the effects of tenoxicam, an oxicam derivative with a thienothiazine structure, on neutrophil activation were evaluated by the assessment of the following parameters: (1) superoxide anion generation by neutrophils and whole blood stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP), the calcium ionophore A23187 and serum treated zymosan (STZ); (2) β-glucuronidase release from neutrophils stimulated with fMLP, A23187 and STZ; (3) binding of [3H]fMLP to intact neutrophils. The results were compared to those obtained using piroxicam and diclofenac. Tenoxicam, added in vitro to whole blood, at concentrations ranging between 10-5 and 3 x 10-4 m, significantly inhibited the generation of superoxide anion induced by fMLP, A23187 and STZ. The activity of tenoxicam on whole blood was similar to that of piroxicam, whereas diclofenac had only minimal effects on this experimental system. In isolated cells tenoxicam inhibited the generation of superoxide anion induced by A23187 and STZ. In addition, at the 3 x 10-4 M concentration, tenoxicam and diclofenac similarly inhibited O2 - generation by neutrophils stimulated with fMLP, whereas piroxicam only minimally affected this parameter. Tenoxicam also slightly, but not significantly, inhibited β-glucuronidase release by isolated neutrophils induced by all the agonists used. Specific binding of [3H]fMLP to neutrophils was inhibited by the three NSAIDs tested in a dose-dependent fashion and tenoxicam was the most potent. The affinities (Kd) of tenoxicam, piroxicam and diclfenac wre 1.11, 1.80 and 2.70 × 10-5 m, respectively. Te mechanism and inhibition of [3H]fMLP binding by tenoxicam was non-competitive. It is concluded that tenoxicam, at concentration achievable in plasma at steady state, effectively inhibits some of the processes involved in the neutrophil activation, which bear some relevane in the inflammatory disease.

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