Gamma and Pulse Radiolysis Study of Pentoxifylline, a Methylxanthine

Abstract

Pentoxifylline (Ptx) is a tri-substituted purine with anti-inflammatory properties which are thought to be due, in part, to oxygen radical scavenging. This paper reports an investigation of the reaction of Ptx with the hydroxyl radical [OH.], superoxide anion, azide radical and hydrogen peroxide generated by pulse and gamma-radiolysis, which was carried out to determine the scavenging properties of Ptx towards oxygen radicals. The superoxide anion, azide radical and hydrogen peroxide did not react with Ptx, whereas OH. reacted rapidly. In gamma-radiolysis, the action of OH. on Ptx at pH 7.4 gave rise to an end-product separated by high-performance liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry as C-8-OH-Ptx (yield 0.12 x 10(-6) mol J-1). The reaction of Ptx with OH. after pulse radiolysis at pH 7-7.4 occurred with a rate constant of (7.7 +/- 1.0) x 10(9) mol-1 s-1, forming time-dependent transient radicals. The initial spectrum (2 microseconds after the pulse) showed three maxima (310, 338 and 500 nm). A decrease in the absorbance around 500 nm and an increase around 310 nm reflected a first-order reaction, suggesting a unimolecular rearrangement. It was shown by redox titration that at least two OH-adducts were formed, one with reducing and the other with oxidizing properties. These results suggest that the reducing radical may be (C-8-OH-Ptx)(.).