Oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage

Journal Article · Thu Dec 01 00:00:00 EST 1988 · Prostaglandins; (United States)

DOI:https://doi.org/10.1016/0090-6980(88)90055-X· OSTI ID:5904700

Peters-Golden, M; Shelly, C

We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of /sup 14/C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-fold and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of /sup 14/C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.

• Research Organization: Univ. of Michigan, Ann Arbor (USA)
• OSTI ID: 5904700
• Journal Information: Prostaglandins; (United States), Vol. 36:6
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ARACHIDONIC ACID
METABOLISM
GOLD COMPOUNDS
BIOCHEMICAL REACTION KINETICS
OXYGENASES
PROSTAGLANDINS
BIOSYNTHESIS
ANTIPYRETICS
CARBON 14 COMPOUNDS
DOSE-RESPONSE RELATIONSHIPS
EICOSANOIC ACID
ENZYME INHIBITORS
IN VITRO
LAVAGE
LIQUID COLUMN CHROMATOGRAPHY
MACROPHAGES
RADIOIMMUNOASSAY
SECRETION
TIME DEPENDENCE
ANIMAL CELLS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
DRUGS
ENZYMES
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MONOCARBOXYLIC ACIDS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
PHAGOCYTES
RADIOASSAY
RADIOIMMUNOLOGY
REACTION KINETICS
SEPARATION PROCESSES
SOMATIC CELLS
SYNTHESIS
TRACER TECHNIQUES
TRANSITION ELEMENT COMPOUNDS
550501* - Metabolism- Tracer Techniques