Ultrasonically induced cell damage and active oxygen generation by 4-formyloximeetylidene-3-hydroxyl-2-vinyl-deuterio-porphynyl(IX)-6-7-diaspartic acid: on the mechanism of sonodynamic activation.
Ultrasonically induced cell damage and active oxygen generation with 4-formyloximeetylidene-3-hydroxyl-2-vinyl-deuterio-porphynyl(IX)-6-7-diaspartic acid (ATX-S10) were compared in the same in vitro insonation setup. Sarcoma 180 cells suspended in air-saturated PBS were exposed to ultrasound at 2 MHz for up to 60 s in the presence and absence of ATX-S10. The viability was determined by Trypan blue exclusion test. Ultrasonically induced active oxygen generation in the presence and absence of ATX-S10 in air-saturated aqueous solutions of 50 mM 2,2,6,6-tetramethyl-4-piperidone was detected by electron spin resonance (ESR). Significant enhancement of the rates of both ultrasonically induced cell damage and nitroxide generation was demonstrated with 40-160 microM ATX-S10. Both rates correlated very well. The enhancement of both rates with ATX-S10 was suppressed by 10 mM histidine. These results suggest that ultrasonically generated active oxygen plays a primary role in the ultrasonically induced cell damage in the presence of ATX-S10.
Yumita
Nagahiko
N
School of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan.
Sakata
Isao
I
Nakajima
Susumu
S
Umemura
Shin-ichiro
S
D000818:Animals; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry; D006639:Histidine / Q000737:chemistry; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000032:analysis / Q000138:chemical synthesis; D011166:Porphyrins / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000032:analysis / Q000737:chemistry*; D012510:Sarcoma 180; D014407:Tumor Cells, Cultured; D014465:Ultrasonics
C115550:ATX-S10; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D011166:Porphyrins; D017382:Reactive Oxygen Species; D006639:Histidine; C039900:nitroxyl