Department of Anesthesiology and Pain Medicine, College of Medicine, Jeju University, Jeju, Korea.
Korean J Anesthesiol. 2010 Sep;59(3):196-202. doi: 10.4097/kjae.2010.59.3.196. Epub 2010 Sep 20.
Reactive oxygen species (ROS) induce lipid peroxidation and tissue damage in endothelium. We studied the influences of ketorolac and diclofenac on ROS effects using the endothelium of rabbit abdominal aorta.
Isolated rabbit aortic rings were suspended in an organ bath filled with Krebs-Henseleit (K-H) solution bubbled with 5% CO(2) and 95% O(2) at 37.5℃. After being stimulated to contract with phenylephrine (PE, 10(-6) M), changes in arterial tension were recorded following the cumulative administration of acetylcholine (ACh, 3 × 10(-8) to 10(-6) M). The percentages of ACh-induced relaxation of aortic rings before and after exposure to ROS, generated by electrolysis of K-H solution, were used as the control and experimental values, respectively. The aortic rings were pretreated with ketorolac or diclofenac at the same concentrations (10(-5) M to 3 × 10(-4) M), and the effects of these agents were compared with the effects of ROS scavengers: catalase, mannitol, sodium salicylate and deferoxamine and the catalase inhibitor, 3-amino-1,2,4-triazole (3AT).
Both ketorolac and diclofenac maintained endothlium-dependent relaxation induced by ACh in a dose-related manner inspite of ROS attack (P < 0.05 vs. control value). The 3AT pretreated ketorolac (3 × 10(-3) M) group was decreased more significantly than un-pretreated ketorolac (P < 0.05).
These findings suggest that ketorlac and diclofenac preserve the endothelium-dependent vasorelaxation against the attack of ROS, in a concentration-related manner. One of the endothelial protection mechanisms of ketorolac may be hydrogen peroxide scavenging.
活性氧（ROS）可导致内皮细胞中的脂质过氧化和组织损伤。我们使用兔腹主动脉内皮研究了酮咯酸和双氯芬酸对 ROS 作用的影响。
将分离的兔主动脉环悬挂在充满 Krebs-Henseleit（K-H）溶液的器官浴中，该溶液用 5%CO₂和 95%O₂在 37.5℃下进行通气。用苯肾上腺素（PE，10⁻⁶ M）刺激动脉环收缩后，记录乙酰胆碱（ACh，3×10⁻⁸ 至 10⁻⁶ M）累积给药后动脉张力的变化。ROS 产生后，用电解 K-H 溶液的方法测量暴露于 ROS 前后主动脉环对 ACh 诱导的舒张百分比，分别作为对照值和实验值。用相同浓度（10⁻⁵ M 至 3×10⁻⁴ M）的酮咯酸或双氯芬酸预处理主动脉环，并将这些药物的作用与 ROS 清除剂（过氧化氢酶、甘露醇、水杨酸钠和去铁胺）和过氧化氢酶抑制剂（3-氨基-1,2,4-三唑[3AT]）的作用进行比较。
尽管 ROS 攻击，酮咯酸和双氯芬酸仍能以剂量相关的方式维持由 ACh 诱导的内皮依赖性舒张（P<0.05 与对照值相比）。与未预处理的酮咯酸相比，用 3AT 预处理的酮咯酸（3×10⁻³ M）组降低更为显著（P<0.05）。
这些发现表明，酮咯酸和双氯芬酸以浓度相关的方式保护内皮细胞免受 ROS 的攻击，从而维持内皮依赖性血管舒张。酮咯酸的一种内皮保护机制可能是清除过氧化氢。
