Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.
Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.
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发表时间：
1990-02
期刊：
影响因子：
11.2
通讯作者：
A. Ferrario;C. Gomer
中科院分区：
文献类型：
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作者：
A. Ferrario;C. Gomer
在 Photofrin II 介导的光动力疗法 (PDT) 治疗（仅限于正常小鼠和荷瘤小鼠的后腿）后，已记录到出乎意料的高水平急性致死率。诱导致死性的 PDT 剂量（10 mg/kg Photofrin II，200-500 J/cm2）处于治愈小鼠肿瘤所需的剂量范围内。致死率与总光剂量成正比，但与传递光的剂量率成反比。在四种色素小鼠品系（C57BL/6J、C3H/HeJ、DBA/1 和 DBA/2）和两种白化小鼠品系（BALB/c 和 Swiss Webster）中观察到了相当水平的急性毒性。在两种色素小鼠品系（B10D2/OSN 和 B10D2/NSN）中观察到对 PDT 诱导致死的敏感性降低。服用华法林、阿司匹林、吲哚美辛或抗组胺药在降低 PDT 引起的致死率方面具有显着的保护作用。然而，注射眼镜蛇毒因子（以消耗补体系统的 C3 和 C5）并没有改变 PDT 介导的致死率。 PDT 后 24 小时获得的组织学特征显示肝脏、肾脏、肺和脾中有血管充血。局部 PDT 治疗 24 小时内还观察到可移动血容量、核心温度和脾脏重量显着下降。这些结果表明，PDT 诱导的致死率与创伤性休克综合征一致，并表明休克的内源性血管活性介质（如前列腺素、血栓素和组胺）与小鼠局部 PDT 诱导的致死率相关。
An unexpected high level of acute lethality has been documented following Photofrin II-mediated photodynamic therapy (PDT) treatments which were localized to the hind leg of normal and tumor-bearing mice. Doses of PDT which induced lethality (10 mg/kg Photofrin II, 200-500 J/cm2) were in the range of doses required to obtain murine tumor cures. The percentage of lethality was proportional to the total light dose but was inversely proportional to the dose rate of delivered light. Comparable levels of acute toxicity were observed in four pigmented mouse strains (C57BL/6J, C3H/HeJ, DBA/1, and DBA/2) and in two albino mouse strains (BALB/c and Swiss Webster). Decreased sensitivity to PDT-induced lethality was observed in two pigmented mouse strains (B10D2/OSN and B10D2/NSN). The administration of warfarin, aspirin, indomethacin, or antihistamine had significant protective effects in terms of decreasing PDT-induced lethality. However, injection of cobra venom factor (to deplete C3 and C5 of the complement system) did not alter the lethality mediated by PDT. Histological profiles obtained 24 h following PDT demonstrated vascular congestion in the liver, kidney, lung, and spleen. Significant decreases in removable blood volume, core temperature, and spleen weight were also observed within 24 h of localized PDT treatment. These results indicate that PDT-induced lethality is consistent with a traumatic shock syndrome and suggest that endogenous vasoactive mediators of shock such as prostaglandins, thromboxanes, and histamine are associated with the lethality induced by localized PDT in mice.