Effects of cysteamine and cystamine on the sonochemical accumulation of hydrogen peroxide - Implications for their mechanisms of action in ultrasound-exposed cells

Based on the observed cytoprotective effect of the intracellularly permeabl e radical scavenger cysteamine (+NH3CH2CH2SH) in cells exposed to ultrasoun d and the lack of protection by its oxidized cell-nonpermeable form, cystam ine (+NH3CH2CH2S-SCH2CH2NH3+), it was suggested that inertial cavitation (t he growth of small gas bubbles present in the liquid exposed to ultrasound and their subsequent violent collapse) and associated free radical producti on may occur intracellularly (Radiat. Res. 89:369; 1982). Here we demonstra te that high concentrations (>10 mM) of the thiol cysteamine effectively lo wer H2O2 yields following ultrasound exposure in argon- and air-saturated p hosphate buffered saline (PBS), while cystamine is less effective under arg on and practically without effect in air-saturated PBS. Direct removal of H 2O2 by cysteamine is the dominant mechanism while scavenging of the H2O2 pr ecursors (OH)-O-. and superoxide plays a lesser role. Since H2O2 is a known cytotoxic species capable of penetrating cells if produced extracellularly , these results offer an alternative hypothesis for the protective effect o f cysteamine and the lack of protection by cystamine, based on their differ ential ability to lower ultrasound-dependent H2O2 yields, without the neces sity of invoking intracellular cavitation. (C) 1999 Elsevier Science Inc.