El-Missiry M A, Abou-Seif M
Zoology Department, Faculty of Science, Mansoura University, 35516, Mansoura, Egypt.
Cancer Lett. 2000 Oct 1;158(2):155-63. doi: 10.1016/s0304-3835(00)00513-9.
Generation of reactive oxygen species by photosensitization is the corner stone of photodynamic therapy of tumors. Cell damage may be mediated by free radical species and lipid peroxidation of their membranes. The effects of oxygen active species (.OH and O(2)(.-) radicals) photogenerated by the novel photosensitizer m-chloroperbenzoic acid (m-CPBA) on human erythrocyte integrity and stability were studied. The biological toxicity of the reactive oxygen species on human red blood cells (RBCs) was evident by increased osmotic fragility, spherocytosis and haemolysis. The haemolysis was increased in concentration and time dependent manner. The lipid peroxidation product thiobarbituric acid reactive substances (TBARS) was elevated in m-CPBA photosensitized RBCs indicating increased oxidative stress. This was accompanied with a depletion of erythrocyte glutathione (GSH). These effects were blunted by hydroxyl radical scavengers, thiourea and mannitol, which might indicate the production of (.)OH radical by photosensitization with m-CPBA. The antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), peroxidase (Px) and glutathione peroxidase (GSH-Px) were elevated in RBCs treated with m-CPBA in the presence and absence of hydroxyl radical scavengers, mannitol and thiourea. These results suggested that the main oxygen radical photogenerated from m-CPBA is O(2)(&z.rad;-) radical, which is transformed to (.)OH radical probably by hydrogen abstraction. This is probably the main damaging oxygen species and played an essential role in oxidative haemolysis mediated by peroxidation of membrane lipids of human erythrocytes. This study provides an investigational promising data for photodynamic therapy.
通过光敏化产生活性氧是肿瘤光动力治疗的基石。细胞损伤可能由自由基及其细胞膜的脂质过氧化介导。研究了新型光敏剂间氯过苯甲酸（m-CPBA）光生成的氧活性物种（·OH和O₂⁻·自由基）对人红细胞完整性和稳定性的影响。活性氧对人红细胞（RBC）的生物毒性表现为渗透脆性增加、球形红细胞增多和溶血。溶血呈浓度和时间依赖性增加。m-CPBA光敏化的红细胞中脂质过氧化产物硫代巴比妥酸反应性物质（TBARS）升高，表明氧化应激增加。这伴随着红细胞谷胱甘肽（GSH）的消耗。羟基自由基清除剂硫脲和甘露醇可减弱这些作用，这可能表明m-CPBA光敏化产生了·OH自由基。在有和没有羟基自由基清除剂甘露醇和硫脲的情况下，用m-CPBA处理的红细胞中超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、过氧化物酶（Px）和谷胱甘肽过氧化物酶（GSH-Px）等抗氧化酶活性升高。这些结果表明，m-CPBA光生成的主要氧自由基是O₂⁻·自由基，它可能通过夺氢转化为·OH自由基。这可能是主要的损伤性氧物种，在人红细胞膜脂质过氧化介导的氧化溶血中起重要作用。本研究为光动力治疗提供了有前景的研究数据。
