安托美汀胍酯对不同胃肠道损伤模型中脂质过氧化和抗氧化防御系统的体内作用。

In vivo effects of amtolmetin guacyl on lipid peroxidation and antioxidant defence systems in different models of gastrointestinal injury.

Kirkova M, Kesiova M, Konstantinova S, Alexandrova A, Petrov L, Tsvetanova E, Todorov S

Institute of Physiology, Bulgarian Academy of Sciences, 23 Acad. G. Bonchev St, 1113 Sofia, Bulgaria.

Auton Autacoid Pharmacol. 2007 Jan;27(1):63-70. doi: 10.1111/j.1474-8673.2006.00390.x.

Abstract

The in vivo effects of the non-steroid anti-inflammatory drug (NSAID) amtolmetin guacyl (AMG) on lipid peroxidation (LP) and on antioxidant enzyme and non-enzyme defence systems were investigated in models of stomach and colon damages, induced by other NSAIDs, by ethanol or by 2,4,6-trinitrobenzenesulfonic acid (TNBS). 2. Indomethacin increased LP, glutathione peroxidase (GSH-PX) and glucose-6-phosphate dehydrogenase (Glu-6-P-DH) activities and decreased glutathione levels in gastric mucosa. Pretreatment with AMG normalized some of the parameters affected by indomethacin. 3. Treatment of rats with ethanol for 0.5 h led to a decrease in glutathione levels as well as activities of glutathione reductase and Glu-6-P-DH in gastric mucosa. AMG, administered 0.5 h before ethanol, limited the adverse actions of ethanol. 4. Amtolmetin guacyl failed to abolish the TNBS-induced changes in the followed-up parameters in colon mucosa and liver, but additional alterations (as with tolmetin) were not observed. 5. The beneficial profile of AMG in the various experimental models of free radical-induced damage investigated in this study suggests the possibility that this drug might possess antioxidant activity.

摘要

在由其他非甾体抗炎药、乙醇或2,4,6-三硝基苯磺酸（TNBS）诱导的胃和结肠损伤模型中，研究了非甾体抗炎药安托美汀胍基（AMG）对脂质过氧化（LP）以及抗氧化酶和非酶防御系统的体内作用。2. 吲哚美辛增加了胃黏膜中的LP、谷胱甘肽过氧化物酶（GSH-PX）和葡萄糖-6-磷酸脱氢酶（Glu-6-P-DH）活性，并降低了谷胱甘肽水平。用AMG预处理可使受吲哚美辛影响的一些参数恢复正常。3. 用乙醇处理大鼠0.5小时导致胃黏膜中谷胱甘肽水平以及谷胱甘肽还原酶和Glu-6-P-DH活性降低。在乙醇处理前0.5小时给予AMG，可限制乙醇的不良作用。4. 安托美汀胍基未能消除TNBS诱导的结肠黏膜和肝脏中后续参数的变化，但未观察到其他改变（如托美汀所致）。5. 本研究中在各种自由基诱导损伤的实验模型中AMG的有益表现表明，该药可能具有抗氧化活性。