arachidonic-acid-omega-9-hydroperoxide and Asthma

Platelets are involved in the pathogenesis of aspirin-induced asthma (AIA). AIA patients suffer from an active disease despite avoidance of aspirin, and it has been suggested that administration of aspirin to these patients increases the generation of immediate oxygen products of arachidonic acid, 12-hydroperoxyeicosatetraenoic acid (12-HPETE), in their platelets. 12-HPETE further activates the 5-lipoxygenase of leukotriene B4-producing inflammatory macrophages precipitating an acute asthmatic attack. Glutathione peroxidase (GPX) has the antioxidant capacity to reduce 12-HPETE, and thus modulate the arachidonic acid metabolic cascade. There is evidence that selenium (Se) nutrition can influence asthma but Se status in AIA patients has not received much attention.. We measured Se concentrations and GPX activities in platelets and plasma from 13 patients with AIA. Age- and sex-matched healthy individuals served as the control group.. Patients with AIA had significantly higher median platelet Se concentration (102 ng/mg platelet protein) when compared with controls (49 ng/mg platelet protein, P = 0.003). Plasma Se concentrations in patients with AIA and controls were not significantly different (P = 0.59). Median platelet GPX activity was significantly higher in patients with AIA (102.7 mU/mg platelet protein) than in controls (66 mU/mg protein) (P = 0.05). The patient and control groups when combined showed weak, but significant correlation between platelet Se concentration and platelet GPX activity (r = 0.44; P = 0.03).. It is proposed that the higher platelet Se concentration observed in AIA patients contributed to the higher platelet GPX activity seen in these patients. Such an enhanced antioxidant defence system might represent an adaptive response to protect against increasing free radical production by inflammatory cells in AIA and help decelerate ongoing respiratory hypersensitivity.

Topics: Adult; Aged; Antioxidants; Arachidonate 5-Lipoxygenase; Arachidonic Acid; Aspirin; Asthma; Female; Free Radicals; Humans; Leukotriene B4; Leukotrienes; Macrophages; Male; Middle Aged; Selenium

Leukotrienes and prostaglandins possess properties which are central in the asthmatic reaction. They are bronchoconstrictors, they inhibit the mucociliary clearance, increase blood flow and permeability and thereby induce edema formation, and they attract and activate leukocytes. They are formed partly by allergic reactions and partly by a large number of other more non-specific reactions. Finally, the concentration of prostanoids has been found increased in the asthmatic reaction in vivo. The leukotrienes have not been traced in vivo in asthmatic attacks so far, but have been found in vivo in man in a specific type I allergic conjunctival reaction. Much evidence suggests that these mediators are relevant in asthmatic diseases, even though prostaglandin inhibitors have no effect in asthma. There still remains the need to investigate the influence on asthmatic diseases by as yet unavailable leukotriene blocking agents. Even though leukotrienes are judged today to be important mediators in asthma, it does not seem reasonable to expect that a single mediator is responsible for asthmatic diseases. Rather, it seems quite likely that asthma is caused by a complex interplay of a large number of mediators, circulating hormones, nervous mechanisms, receptor abnormalities, intracellular metabolic defects, etc. Despite this complexity, investigations in recent years have increased the knowledge of the biochemistry and human physiological effects of leukotrienes and prostaglandins which has created an improved understanding of the asthmatic reaction's pathophysiology, contributed a pharmacological rationale for previously used therapy, and stimulated new perspectives for specific pharmacological research.

Topics: Anti-Inflammatory Agents; Arachidonic Acid; Arachidonic Acids; Asthma; Autacoids; Bronchial Spasm; Ciliary Motility Disorders; Cyclooxygenase Inhibitors; Edema; Enzyme Inhibitors; Histamine Release; Humans; Leukotriene B4; Leukotrienes; Mast Cells; Prostaglandins