Baas P, Oppelaar H, van der Valk M A, van Zandwijk N, Stewart F A
Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
Photochem Photobiol. 1994 Apr;59(4):448-54. doi: 10.1111/j.1751-1097.1994.tb05063.x.
The major side effect of photodynamic therapy (PDT) using Photofrin is enhanced skin sensitivity for sunlight, which persists for 3-8 weeks after injection. Formation of singlet oxygen and radicals is believed to be involved in the basic mechanism of inducing skin damage. Reducing this side effect would make PDT more widely acceptable, particularly for palliative use. Hairless dorsal skin patches of mice, injected with 10 mg kg-1 photofrin intraperitoneally (i.p.) 24 h before illumination, were used to evaluate the effect of increasing light doses. The light was obtained from a halogen lamp and transmitted via a fiber optic to illuminate a field of 2.5 cm2. After establishing a dose-response relationship for single or fractionated light dose illumination of the skin, drugs known to scavenge radicals, quench singlet oxygen or interfere with histamine release were tested for their protective effect. N-acetyl-cysteine (NAC), a radical scavenger, administered i.p. (1000 and 2000 mg kg-1) 1 h before illumination produced a significant decrease in skin damage at light doses > 50 J cm-2 (protection factor of 1.3-1.8). When NAC was administered in a dose of 500 mg kg-1, no protection was observed. Fractionated illumination experiments in combination with multiple injections of NAC (1000 mg kg-1) also failed to show any protection. The addition of Ranitidine, a histamine blocking agent (25-100 mg kg-1), given prior to illumination, resulted in a limited protection at higher light doses. From this study we conclude that NAC could be of value in amelioration of the photosensitivity in patients treated with PDT.
使用卟吩姆钠进行光动力疗法（PDT）的主要副作用是皮肤对阳光的敏感性增强，这种敏感性在注射后会持续3 - 8周。单线态氧和自由基的形成被认为参与了诱导皮肤损伤的基本机制。减少这种副作用将使PDT更广泛地被接受，特别是在姑息治疗中。在光照前24小时腹腔注射（i.p.）10 mg/kg卟吩姆钠的无毛小鼠背部皮肤贴片，用于评估增加光剂量的效果。光由卤素灯发出，并通过光纤传输以照亮2.5平方厘米的区域。在建立皮肤单次或分次光剂量照射的剂量反应关系后，测试了已知能清除自由基、淬灭单线态氧或干扰组胺释放的药物的保护作用。自由基清除剂N - 乙酰半胱氨酸（NAC）在光照前1小时腹腔注射（1000和2000 mg/kg），在光剂量>50 J/cm²时可显著减少皮肤损伤（保护因子为1.3 - 1.8）。当NAC以500 mg/kg的剂量给药时，未观察到保护作用。与多次注射NAC（1000 mg/kg）相结合的分次光照实验也未显示出任何保护作用。在光照前给予组胺阻断剂雷尼替丁（25 - 100 mg/kg），在较高光剂量下可产生有限的保护作用。从这项研究中我们得出结论，NAC可能对改善接受PDT治疗患者的光敏性有价值。
