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中-四[3,4-双(羧基亚甲基氧基)苯基]卟啉在肝微粒体和肿瘤微粒体光敏化过程中诱导的脂质过氧化作用

Lipid peroxidation induced by meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl] porphyrin on photosensitization in hepatic and tumor microsomes.

作者信息

Chatterjee S R, Srivastava T S, Kamat J P, Devasagayam T P

机构信息

Department of Chemistry, Indian Institute of Technology, Mumbai, India.

出版信息

Chem Biol Interact. 1997 Dec 12;108(1-2):27-37. doi: 10.1016/s0009-2797(97)00092-6.

DOI:10.1016/s0009-2797(97)00092-6
PMID:9463519
Abstract

The ability of a novel porphyrin, meso-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin (T3,4-CPP), to induce photodamage in subcellular membranes, in the form of rat hepatic and tumor microsomes, was evaluated with a view to locating suitable porphyrin derivative for possible use in photodynamic therapy. This water-soluble porphyrin, on exposure to visible light, induced a significant extent of membrane lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes. The peroxidation induced in hepatic microsomes is both time- and concentration-dependent. Using inhibitors of reactive oxygen species and comparing products of peroxidation, it is shown that the damage induced is mainly due to singlet oxygen and partly due to other species like free radicals. T3,4-CPP also caused the generation of singlet oxygen as a function of illumination time. Since membrane damage induced by a sensitizer on photoexcitation has been considered to be an important mechanism by which photodynamic cell killing of tumor occurs, the studies on this novel porphyrin indicate the possible potential of this compound in photodynamic therapy.

摘要

为了找到适合用于光动力疗法的卟啉衍生物,评估了一种新型卟啉——中-四[3,4-双(羧基亚甲基氧基)苯基]卟啉(T3,4-CPP)以大鼠肝脏和肿瘤微粒体形式在亚细胞膜中诱导光损伤的能力。这种水溶性卟啉在可见光照射下,通过硫代巴比妥酸反应性物质、脂质氢过氧化物和共轭二烯的形成评估,诱导了显著程度的膜脂质过氧化。肝脏微粒体中诱导的过氧化反应具有时间和浓度依赖性。使用活性氧抑制剂并比较过氧化产物,结果表明诱导的损伤主要归因于单线态氧,部分归因于自由基等其他物质。T3,4-CPP还会随着光照时间产生单线态氧。由于敏化剂在光激发时诱导的膜损伤被认为是肿瘤光动力细胞杀伤发生的重要机制,对这种新型卟啉的研究表明该化合物在光动力疗法中可能具有潜力。

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