Karbownik M, Reiter R J, Garcia J J, Cabrera J, Burkhardt S, Osuna C, Lewiński A
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas.
J Cell Biochem. 2001;81(3):507-13.
Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl(3) (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe(3+) was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe(3+) was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe(3+)-induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.
过量的游离铁及相关的氧化损伤通常与癌症发生有关。在已知可防止铁诱导的氧化损伤和癌症发生的抗氧化剂中，褪黑素和其他吲哚化合物最近受到了相当多的关注。吲哚 - 3 - 丙酸（IPA）是色氨酸的脱氨基产物，其结构与褪黑素相似，存在于生物体液中，是一种有效的自由基清除剂。本研究的目的是检测IPA对实验诱导的大鼠肝微粒体膜氧化变化的影响。微粒体在IPA（10、3、2、1、0.3、0.1、0.01或0.001 mM）存在下预孵育，然后与FeCl₃（0.2 mM）、ADP（1.7 mM）和NADPH（0.2 mM）一起孵育以诱导氧化损伤。通过荧光光谱法估计膜流动性（膜刚性的倒数）的变化，并通过测量丙二醛 + 4 - 羟基烯醛（MDA + 4 - HDA）的浓度来检测脂质过氧化。当以10、3或2 mM的浓度使用时，IPA增加了膜流动性，尽管在这些浓度下它对脂质过氧化没有显著影响。在10、3、2或1 mM浓度的IPA存在下预孵育可完全防止由于Fe³⁺导致的膜流动性降低。仅在最高浓度（10 mM）时，IPA可防止由于Fe³⁺导致的脂质过氧化增强。结论是，IPA可能会降低Fe³⁺诱导的微粒体膜刚性以及在较小程度上降低脂质过氧化。然而，高浓度的IPA会增加膜流动性。除了褪黑素外，IPA可作为一种药物制剂来防止铁诱导的膜氧化损伤，并可能预防癌症发生。
