Metalloporphyrins are potent inhibitors of lipid peroxidation
Metalloporphyrins are potent inhibitors of lipid peroxidation
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DOI：
10.1016/s0891-5849(98)00261-5
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发表时间：
1999-03-01
影响因子：
7.4
通讯作者：
Crapo, JD
中科院分区：
文献类型：
--
作者：
Day, BJ;Batinic-Haberle, I;Crapo, JD
这些研究的目的是确定金属卟啉是否可以抑制脂质过氧化，表征影响其效力的因素，并将其与典型抗氧化剂的效力进行比较。用大鼠脑匀浆中的铁和抗坏血酸引发脂质过氧化，并使用硫代巴比妥酸反应物的形成作为脂质过氧化的指标。金属卟啉被发现是一类新型且有效的脂质过氧化抑制剂。金属卟啉对脂质过氧化的抑制取决于连接到卟啉的过渡金属，表明以金属为中心的氧化还原化学对其抗氧化活性机制很重要。具有最高超氧化物歧化酶 (SOD) 活性的锰卟啉 MnOBTM-4-PyP 和 MnTM-2-PyP（为清楚起见，在整个文本中省略了电荷）是最有效的脂质过氧化抑制剂，计算出的 IC(50) 分别为 1.3 和 1.0 μM。这些锰卟啉的效力比 trolox (IC50 = 204 muM) 或芦丁 (IC50 = 112 muM) 强 2 个数量级。锰卟啉的效力不仅与其氧化还原电位和 SOD 活性有关，还与可能有助于其充当电子受体的能力的其他因素有关。金属卟啉具有广泛的抗氧化活性，使其成为涉及活性氧过度产生的疾病状态的有吸引力的治疗剂。 (C) 1999 爱思唯尔科学公司。
The objectives of these studies were to determine whether metalloporphyrins could inhibit lipid peroxidation, characterize factors that influence their potency and compare their potency to prototypical antioxidants. Lipid peroxidation was initiated with iron and ascorbate in rat brain homogenates and the formation of thiobarbituric acid reactive species was used as an index of Lipid peroxidation. Metalloporphyrins were found to be a novel and potent class of lipid peroxidation inhibitors. Inhibition of lipid peroxidation by metalloporphyrins was dependent on the transition metal ligated to the porphyrin, indicating that metal centered redox chemistry was important to the mechanism of their antioxidant activities. Manganese porphyrins with the highest superoxide dismutase (SOD) activities, MnOBTM-4-PyP and MnTM-2-PyP (charges are omitted throughout text for clarity), were the most potent inhibitors of lipid peroxidation with calculated IC(50)s of 1.3 and 1.0 mu M, respectively. These manganese porphyrins were 2 orders of magnitude more potent than either trolox (IC50 = 204 mu M) or rutin (IC50 = 112 mu M). The potencies of the manganese porphyrins were related not only to their redox potentials and SOD activities, but also to other factors that may contribute to their ability to act as electron accepters. The broad array of antioxidant activities possessed by metalloporphyrins make them attractive therapeutic agents in disease states that involve the overproduction of reactive oxygen species. (C) 1999 Elsevier Science Inc.