Hydroxylation of salicylate by activated neutrophils

W. Bruce Davis, B. Selma Mohammed, Dennis C. Mays, Zhi Wu She, Jeannette R. Mohammed, Rose M. Husney, Arthur L. Sagone

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Salicylates are metabolized in vivo to hydroxylated compounds, including 2,3-dihydroxy-benzoic acid and 2,5-dihydroxybenzoic acid (gentisic acid). The present study hypothesized that activated neutrophils represent one pathway for salicylate hydroxylation. Human neutrophils were incubated in medium containing 10 mM salicylate and stimulated with phorbol myristate acetate (PMA) for 1 hr. The cell-free supernatant fractions were analyzed by HPLC. Neutrophils (1 × 106 cells) produced 55 ± 11 ng of gentisic acid. Neutrophils also produced smaller quantities of 2,3-dihydroxybenzoic acid. Antioxidant inhibitor experiments indicated that superoxide dismutase (SOD), heme protein inhibitors, and glutathione blocked gentisic acid formation, whereas catalase, mannitol, and deferoxamine failed to inhibit. Experiments with the reagent hypochlorous acid (HOCl) and the model myeloperoxidase (MPO) enzyme system did not support a role for the MPO pathway in gentisic acid formation. These findings demonstrate that activated neutrophils can hydroxylate salicylate by an unknown pathway. This pathway may contribute to the increased recovery of hydroxylated salicylates in patients with inflammatory disorders.

Original languageEnglish (US)
Pages (from-to)4013-4019
Number of pages7
JournalBiochemical Pharmacology
Volume38
Issue number22
DOIs
StatePublished - Nov 15 1989

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Hydroxylation
Salicylates
Neutrophils
Peroxidase
Hemeproteins
Hypochlorous Acid
Deferoxamine
Mannitol
Tetradecanoylphorbol Acetate
Catalase
Superoxide Dismutase
Glutathione
Antioxidants
Experiments
High Pressure Liquid Chromatography
2,5-dihydroxybenzoic acid
Recovery
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

Bruce Davis, W., Selma Mohammed, B., Mays, D. C., She, Z. W., Mohammed, J. R., Husney, R. M., & Sagone, A. L. (1989). Hydroxylation of salicylate by activated neutrophils. Biochemical Pharmacology, 38(22), 4013-4019. https://doi.org/10.1016/0006-2952(89)90681-3

Hydroxylation of salicylate by activated neutrophils. / Bruce Davis, W.; Selma Mohammed, B.; Mays, Dennis C.; She, Zhi Wu; Mohammed, Jeannette R.; Husney, Rose M.; Sagone, Arthur L.

In: Biochemical Pharmacology, Vol. 38, No. 22, 15.11.1989, p. 4013-4019.

Research output: Contribution to journalArticle

Bruce Davis, W, Selma Mohammed, B, Mays, DC, She, ZW, Mohammed, JR, Husney, RM & Sagone, AL 1989, 'Hydroxylation of salicylate by activated neutrophils', Biochemical Pharmacology, vol. 38, no. 22, pp. 4013-4019. https://doi.org/10.1016/0006-2952(89)90681-3
Bruce Davis W, Selma Mohammed B, Mays DC, She ZW, Mohammed JR, Husney RM et al. Hydroxylation of salicylate by activated neutrophils. Biochemical Pharmacology. 1989 Nov 15;38(22):4013-4019. https://doi.org/10.1016/0006-2952(89)90681-3
Bruce Davis, W. ; Selma Mohammed, B. ; Mays, Dennis C. ; She, Zhi Wu ; Mohammed, Jeannette R. ; Husney, Rose M. ; Sagone, Arthur L. / Hydroxylation of salicylate by activated neutrophils. In: Biochemical Pharmacology. 1989 ; Vol. 38, No. 22. pp. 4013-4019.
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