In vitro release of arachidonic acid metabolites, glutathione peroxidase, and oxygen-free radicals from platelets of asthmatic patients with and without aspirin intolerance.

Abstract

Background -An abnormal platelet release of oxygen-free radicals has been described in acetylsalicylic acid (aspirin)-induced asthma, a finding which might suggest the existence of an intrinsic, specific platelet abnormality of arachidonic acid metabolism in these patients. The objective of this study was to evaluate platelet arachidonic acid metabolism in asthmatic patients with or without intolerance to aspirin. Methods -Thirty subjects distributed into three groups were studied: group 1, 10 healthy subjects; group 2, 10 asthmatic patients with aspirin tolerance; and group 3, 10 aspirin-intolerant asthmatics. Platelets were isolated from blood, preincubated with 3H-arachidonic acid for 30 minutes and then incubated for 10minutes with platelet activating factor (PAF) and aspirin. Cyclo-oxygenase (thromboxane, PGE2, PGF2a, and HHT) and lipoxygenase (12-HETE) arachidonic acid metabolites were measured by high pressure liquid chromatography. Release of oxygen free radicals after incubation with PAF and aspirin was measured by chemiluminescence. Platelet levels of glutathione peroxidase (GSH-Px) were also measured using spectrophotometry. Results -Platelets from aspirin-intolerant asthmatic patients produced higher quantities of arachidonic acid metabolites than the control group at baseline conditions. This increase was significant only for lipoxygenase products. No differences were found amongst the three groups in the response of arachidonic acid metabolism to PAF and aspirin. Incubation with aspirin but not with PAF caused an increase in oxygen-free radical production in aspirin-intolerant patients whereas in aspirin-tolerant patients PAF, rather than aspirin, was the more potent stimulus for oxygen-free radical production. No differences in GSH-Px levels were found amongst the three groups.Conclusions -These results suggest that the platelet lipoxygenase pathway is activated in aspirin-intolerant patients and that the production ofoxygen-free radicals may differentiate aspirin-tolerant from aspirin-intolerant asthmatic subjects. Our study, however, does not support the hypothesis that an increase in lipoxygenase products may be responsible for oxygenfree radical production. Moreover, a lowered platelet GSH-Px activity does not seem to be involved in this phenomenon. (Thorax 1995;50:490-496)

Glutathione peroxidase activity and mRNA expression in eosinophils and neutrophils of asthmatic and non-asthmatic subjects

“…Previous studies have shown that peripheral blood and platelet GSH-Px activities are reduced in aspirin-sensitive asthmatic patients [12][13][14][15] and some, but not all, studies have also demonstrated this in atopic asthmatic patients [15][16][17][18][19]. In our study of an Australian population, we showed that reduced GSH-Px activity was associated with reduced serum Se concentrations in atopic asthmatic patients, although the reasons for the reduced Se levels remain unclear [17].…”

Expression of melatonin in platelets of patients with aspirin-induced asthma

“…This results in disturbances in calcium homoeostasis, which in their turn may cause the platelet activation, elevation of the Ca 2+ response to the minimal dose of melatonin in vitro in patients with AIA and striking deviations of platelet shape and ultrastructure found in patients with AIA [6,17]. A low platelet generation of melatonin in patients with AIA may also result in increased lipid peroxidation in platelets, which is consistent with published data on reduced platelet glutathione peroxidase activity and increased reactive oxygen species production in patients with AIA [18–21].…”

“…European Journal of Clinical Investigation Vol 41 783 platelet generation of melatonin in patients with AIA may also result in increased lipid peroxidation in platelets, which is consistent with published data on reduced platelet glutathione peroxidase activity and increased reactive oxygen species production in patients with AIA [18][19][20][21]. Thus, taking into account that platelets are one of the main extrapineal sources of melatonin in human organism, the defect of their membrane receptor organization resulting in lower production of melatonin in AIA provides another evidence of a major role of platelets in this form of bronchial asthma.…”

Blood clots in vessels surrounding symptomatic nerve roots in disc herniation patients: a pilot study

“…Platelets play an important role in acute myocardial infarction [9], in inflammatory diseases such as rheumatoid arthritis [33] and in bronchial asthma [15,28]. According to the results of our study, platelets may also be involved in mechanisms of sciatica.…”