Differential inhibition by nedocromil sodium of superoxide generation elicited by platelet activating factor in human neutrophils

Abstract

Nedocromil sodium (10(-10) - 10(-9) M) produced a dose-related inhibition of superoxide anion generation induced by platelet activating factor (PAF) in human polymorphonuclear leukocytes (PMNs). At a higher concentration (3 x 10(-7) M), nedocromil sodium significantly inhibited superoxide generation elicited by N-formyl-methionyl-leucylphenylalanine, but was unable to block the response to phorbol dibutyrate. Nedocromil sodium (10(-11) - 10(-5) M) enhanced PAF-stimulated lysozyme release in a non-concentration-dependent manner, and was completely ineffective in depressing PAF-induced release of [3H]arachidonic acid and the rise in cytosolic Ca2+. The preferential inhibitory effects of nedocromil sodium on PAF-induced activation of superoxide generation may provide insight into the therapeutic action of this drug as an anti-asthmatic agent.

Neutrophil–induced human bronchial hyper responsiveness in vitro—pharmacological modulation

“…A variety of other products are released from activated neutrophils and any of these may have been responsible for inducing the bronchial hyperresponsiveness observed in vitro. Superoxides [4], lysosomal enzymes [20] and proteases [21] are released when neutrophils are activated by a variety of stimuli, particularly the bacterial chemotactic factor FMLP. Whether these products are involved in the increased responsiveness is not known as yet.…”

“…Whilst we can induce a state of hyperresponsiveness in human tissue we do not know whether anti-inflammatory medieation proposed for asthma therapy can affect this in vitro hyperresponsiveness. One compound of particular interest is nedoeromil sodium, though its mechanism of action has not yet been fully explained, beeause it has inhibitory activity in animal models of induced hyperresponsiveness [3] as well as against many inflammatory eells [4]. It would therefore be of interest to investigate the effeet ofthis eompound in In our original studies [2], calcium ionophore was used to stimulate cells.…”

Oxidative Stress in Chronic Obstructive Pulmonary Disease

“…Nedocromil sodium inhibited O f production by PMN in vitro (261). Ambroxol is an expectorant with antioxidant properties that stimulates the formation and release of surfactant by type II pneumocytes (262,263).…”

Cromoglycate and nedocromil enhanced the reactive oxygen species‐dependent suppressions with, but not without, dexamethasone in ischaemic and histamine paw oedema of mice

“…10 Nedocromil is thus believed to possess an anti-in ammatory character. Inhibition by nedocromil of superoxide radical (O 2 -) generation in human neutrophils 11 and of activation of mast cells, macrophages, eosinophils and epithelial cells 12 also showed this character. The results of a clinical doublebind, placebo-controlled comparison with salbutamol, showed that nedocromil equipotently decreased airway in ammation.…”