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非甾体抗炎药和对乙酰氨基酚对人红细胞氧化应激相关参数的体外作用。

In vitro effects of NSAIDS and paracetamol on oxidative stress-related parameters of human erythrocytes.

作者信息

Orhan H, Sahin G

机构信息

Department of Toxicology, Pharmacy Faculty of Hacettepe University, Ankara, Turkey.

出版信息

Exp Toxicol Pathol. 2001 Jun;53(2-3):133-40. doi: 10.1078/0940-2993-00179.

Abstract

In vitro effects of widely used nonsteroidal antiinflammatory drugs (NSAIDs) and paracetamol were studied on oxidative stress-related parameters of human red blood cells (RBC). Membrane lipid integrity, activity of erythrocyte antioxidant enzymes; i.e. glutathione S-transferase (GST), selenium dependent-glutathione peroxidase (Se-GPx), and catalase (CAT), and hemolytic/stabilizing action of the drugs on erythrocyte membrane were assessed. Diclofenac, indomethacin and paracetamol at the therapeutic and higher concentrations, and dipyrone at the high concentration exerted a statistically significant inhibition on H2O2 forced erythrocytic membrane lipid peroxidation (EMLP). Increased hemolysis was observed by Na-salicylate, naproxen and ketorolac at therapeutic and higher concentrations, and by diclofenac and tiaprofenic acid at high concentrations, while the others seemed to stabilize the membrane at the same conditions. Na-salicylate inhibited GST activity at the therapeutic dose, however activated the same enzyme at high concentrations. Naproxen, tiaprofenic acid and piroxicam caused a decrease in GST activity at therapeutic doses. Paracetamol caused an activation at a high dose. Tiaprofenic acid, ketorolac, naproxen and piroxicam caused a significant Se-GPx inhibition. Erythrocyte CAT activity was increased by Na-salicylate, acemetacin, and tenoxicam at the therapeutic, and by dipyrone at the high concentration. Our results suggest that NSAIDs and paracetamol may be involved in oxidative/antioxidative processes of human erythrocytes. Also, the in vitro EMLP method can be considered as a simple test for evaluating possible antioxidant potency of chemicals.

摘要

研究了广泛使用的非甾体抗炎药(NSAIDs)和对乙酰氨基酚对人红细胞(RBC)氧化应激相关参数的体外作用。评估了膜脂质完整性、红细胞抗氧化酶的活性,即谷胱甘肽S-转移酶(GST)、硒依赖性谷胱甘肽过氧化物酶(Se-GPx)和过氧化氢酶(CAT),以及药物对红细胞膜的溶血/稳定作用。双氯芬酸、吲哚美辛和对乙酰氨基酚在治疗浓度和更高浓度下,以及安乃近在高浓度下对H2O2诱导的红细胞膜脂质过氧化(EMLP)具有统计学显著抑制作用。在治疗浓度和更高浓度下,水杨酸钠、萘普生和酮咯酸,以及在高浓度下双氯芬酸和噻洛芬酸均观察到溶血增加,而其他药物在相同条件下似乎能稳定细胞膜。水杨酸钠在治疗剂量下抑制GST活性,但在高浓度下激活相同的酶。萘普生、噻洛芬酸和吡罗昔康在治疗剂量下导致GST活性降低。对乙酰氨基酚在高剂量下引起激活。噻洛芬酸、酮咯酸、萘普生和吡罗昔康导致Se-GPx显著抑制。水杨酸钠、阿西美辛和替诺昔康在治疗浓度下,以及安乃近在高浓度下使红细胞CAT活性增加。我们的结果表明,NSAIDs和对乙酰氨基酚可能参与人红细胞的氧化/抗氧化过程。此外,体外EMLP方法可被视为评估化学物质可能的抗氧化效力的一种简单测试。

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