Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen
Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen
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DOI：
10.1016/j.freeradbiomed.2005.12.016
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发表时间：
2006-04-15
影响因子：
7.4
通讯作者：
Banerjee, RK
中科院分区：
文献类型：
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作者：
Chattopadhyay, I;Bandyopadhyay, U;Banerjee, RK
本研究探讨了吲哚美辛诱导的活性氧（ROS）致胃溃疡的机制及姜黄素的胃保护作用。姜黄素剂量依赖性地阻断吲哚美辛诱导的胃损伤，在25 mg/kg时显示82%的保护。吲哚美辛诱导的ROS氧化损伤，如增加脂质过氧化和巯基耗尽所示，几乎完全被姜黄素阻断。吲哚美辛导致羟自由基（（OH）-O-中心点）增加近5倍，胃粘膜过氧化物酶显著失活，从而升高内源性H2 O2和H2 O2衍生的（OH）-O-中心点，这被姜黄素阻止。体外研究表明，吲哚美辛仅在H2 O2存在下通过作为自杀底物不可逆地灭活过氧化物酶。5，5-二甲基吡咯啉-N-氧化物（DMPO）保护过氧化物酶，表明吲哚美辛自由基参与失活。吲哚美辛自由基在过氧化物酶-吲哚美辛-H_2O_2体系中以DMPO加合物形式存在（a（N）= 15 G，a（β）（H）= 16 G）。姜黄素以浓度依赖性方式保护过氧化物酶，并消耗H2 O2作为过氧化物酶的合适底物进行氧化，从而阻断吲哚美辛氧化。姜黄素在体外也能抑制（OH）-O-中心点。我们认为姜黄素通过有效清除H2 O2和H2 O2衍生的（OH）-O-中心点，防止吲哚美辛引起的过氧化物酶失活，从而保护胃损伤。(c)2005年爱思唯尔公司All rights reserved.
We have investigated the mechanism of indomethacin-induced gastric ulcer caused by reactive oxygen species (ROS) and the gastroprotective effect of curcumin thereon. Curcumin dose-dependently blocks indomethacin-induced gastric lesions, showing 82% protection at 25 mg/kg. Indomethacin-induced oxidative damage by ROS as shown by increased lipid peroxidation and thiol depletion is almost completely blocked by curcumin. Indomethacin causes nearly fivefold increase in hydroxyl radical ((OH)-O-center dot) and significant inactivation of gastric mucosal peroxidase to elevate endogenous H2O2 and H2O2-derived (OH)-O-center dot, which is prevented by curcumin. In vitro studies indicate that indomethacin inactivates peroxidase irreversibly only in presence of H2O2 by acting as a Suicidal substrate. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) protects the peroxidase, indicating involvement of indomethacin radical in the inactivation. Indomethacin radical was also detected in the peroxidase-indomethacin-H2O2 system as DMPO adduct (a(N) = 15 G, a(beta)(H) = 16 G) by electron spin resonance spectroscopy. Curcumin protects the peroxidase in a concentration-dependent manner and consumes H2O2 for its oxidation as a suitable substrate of the peroxidase, thereby blocking indomethacin oxidation. Curcumin can also scavenge (OH)-O-center dot in vitro. We suggest that curcumin protects gastric damage by efficient removal of H2O2 and H2O2-derived (OH)-O-center dot by preventing peroxidase inactivation by indomethacin. (c) 2005 Elsevier Inc. All rights reserved.