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Interactions of αNi 3 S 2 with Guinea pig alveolar macrophages and liberation of inflammatory mediators
Author(s) -
Teissier E.,
Shirali P.,
Hannothiaux M. H.,
Marez T.,
Haguenoer J. M.
Publication year - 1994
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.2550140304
Subject(s) - arachidonic acid , lipid peroxidation , glutathione , chemistry , malondialdehyde , biochemistry , leukotriene , lipoxygenase , leukotriene b4 , linoleic acid , antioxidant , medicine , inflammation , fatty acid , enzyme , asthma
Our previous investigation presented evidence of interaction between αNi 3 S 2 and membranous and cellular lipids of lung cells, resulting in significant increases in linoleic, linolenic and arachidonic acids. The present work was designed to follow the metabolic fate of arachidonic acid in αNi 3 S 2 ‐exposed guinea pig alveolar macrophages (GPAM) in culture (50 μM αNi 3 S 2 for 3 days). The metabolites of arachidonic acid were assessed by HPLC coupled with UV or electrochemical detection. The concentrations of malondialdehyde (MDA), hydroxyeicosatetraenoic acid (HETE), leucotrienes (LT) and reduced glutathione (GSH) were measured. In exposed cells a significant increase of MDA, a breakdown product of lipid peroxidation, was observed. In addition, the enzymatic reduction of 5‐hydroperoxyeicosatetraenoic acid (5‐HPETE) by the associated oxidation of GSH to GSSG increased 5‐HETE in GPAM cells and decreased GSH. 5‐Hydroperoxyeicosatetraenoic acid was furthermore converted to epoxides, such as leucotriene A4, and we also quantified in exposed cells a signficant increase of its subsequent catabolites LTB 4 , LTC 4 and LTE 4 . Direct measurements of MDA and other metabolites of arachidonic acid clearly show that exposure of GPAM cells to αNi 3 S 2 enhances lipid peroxidation. This lipid peroxidation is an autocatalytic free‐radical process and could be responsible for DNA damage. Furthermore, αNi 3 S 2 intoxication induces the release of proinflammatory products, such as leucotrienes, and the decrease of glutathione.