Aminophylline: could it act as an antioxidant in vivo?
Potential antioxidant properties of aminophylline and theophylline were investigated. We have found that these drugs, though ineffective against superoxide anion and hydrogen peroxide, are scavengers of hydroxyl radical (OH.). Indeed, second-order rate constants (k) of aminophylline and theophylline with OH. are about 1.9 x 10(10) mol-1 s-1 and 4.5 x 10(9) mol-1 s-1, respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to this marked OH. scavenging activity, since it is characterized by a high k value, i.e. about 8 x 10(9) mol-1 s-1. However, when using therapeutically relevant concentrations of the methylxanthines (9 and 13 micrograms mL-1), significant antioxidant effects against OH.-induced oxidant injury are evident only with aminophylline. Although all three substances can apparently bind and inactivate iron, only aminophylline is effective at 9 and 13 micrograms mL-1; also this action is favoured by ethylenediamine. Moreover, therapeutic concentrations of aminophylline, but not of theophylline, are capable of antagonizing hypochlorous acid (HOCl); this effect is entirely due to the presence of ethylenediamine. Oxidant species, such as OH. and HOCl, have been implicated in the pathophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidant properties, which are partly or totally attributable to ethylenediamine, depending on the chemical identity of the prooxidant antagonized (e.g. iron/OH. or HOCl). Aminophylline antioxidant capacity should be taken into account when investigating the lung epithelial lining fluid antioxidant capacity and oxidative stress indices in humans.
Lapenna
D
D
Istituto di Fisiopatologia Medica, Universitá degli Studi G. D. Annunzio, Facoltá di Medicina e Chirurgia, Chieti, Italy.
De Gioia
S
S
Mezzetti
A
A
Ciofani
G
G
Festi
D
D
Cuccurullo
F
F
D000628:Aminophylline / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D003855:Deoxyribose; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers; D006801:Humans; D017665:Hydroxyl Radical; D006997:Hypochlorous Acid; D008168:Lung / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D012680:Sensitivity and Specificity; D013806:Theophylline / Q000494:pharmacology; D017392:Thiobarbituric Acid Reactive Substances
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D000628:Aminophylline; D017665:Hydroxyl Radical; D003855:Deoxyribose; D006997:Hypochlorous Acid; D013806:Theophylline