AMINOPHYLLINE - COULD IT ACT AS AN ANTIOXIDANT IN-VIVO

Potential antioxidant properties of aminophylline and theophylline wer e investigated. We have found that these drugs, though ineffective aga inst superoxide anion and hydrogen peroxide, are scavengers of hydroxy l radical (OH .). Indeed, second-order rate constants (k) of aminophyl line and theophylline with OH . are about 1.9 x 10(10) mol(-1) s(-1) a nd 4.5 x 10(9) mol(-1) s(-1), respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to th is 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 thera peutically relevant concentrations of the methylxanthines (9 and 13 mu g mL(-1)), significant antioxidant effects against OH .-induced oxida nt injury are evident only with aminophylline. Although ah three subst ances can apparently bind and inactivate iron, only aminophylline is e ffective at 9 and 13 mu g mL(-1); also this action is favoured by ethy lenediamine. Moreover, therapeutic concentrations of aminophylline, bu t 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 pat hophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidan t properties, which are partly or totally attributable to ethylenediam ine, 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 flui d antioxidant capacity and oxidative stress indices in humans.