The Antioxidant Effects of Propofol in Menadione-Induced Oxidative Stress in Human Monocyte THP-1 Cells

Propofol在人類單核白血球THP-1細胞面臨Menadione造成氣化壓力傷朗時的抗氣化保護作用

洪健朗(Chian-Lang Hong) ； 陳俊憲(Ching-Hsein Chen) ； 張雯惠(Wen-Huei Chang) ； 呂鋒洲(Fung-Jou Lu) ； 林婉蓁(Wan-Chen Lin) ； 張依婷(Yi-Tin Chang) ； 陳祈宏(Chi-Home Chen) ； 黃仲衡(Chung-Hang Wong)

《重症醫學雜誌》 11卷3期 (2010/10) Pp. 151-160

https://doi.org/10.30035/TCCM.201010.0001

摘要

研究目的：Propofol，thiopental，citosol與midazolam是在重症加護病房中常用於鎮靜安眠的靜脈肴入鎮靜藥物。這些病人常面臨各式各樣的氧化壓力與自由基損傷，尤其需要抗氧化劑以幫助抵抗自由基的傷害。因此這些常用的靜脈注入鎮靜藥物的抗氧化能力更顯現其重要性。本實驗即設計以評估這些臨床上常被使用的藥物的抗氧化特性。
方法：經由透過Menadione，Hydrogen peroxide及Cumene hydroperoxide在人類單核白血球THP-1細胞誘導產生氧化壓力傷害，我們利用流式細胞儀去評估propofol，thiopental，citosol，及midazolam對THP-1細胞面對氧化壓力狀態的保護作用上，做一香釐清與探討。
結果：在上述四種鎮靜藥物中，Propofol可以明顯抑制menadione處裡THP-1細胞內超氧自由基的濃度；也可以有效地抑制細胞內GSH的減少及細胞內粒線體膜電位(△Ψ(下標 m))的下降。Menadione處理THP-1細胞會抑制超氧歧化酶(superoxide dismutase, SOD)與伽瑪－glutamylcysteine合成酶(gamma-glutamylcysteine synthetase，y-GCS)二種抗氧化酵素的表現，而細胞前處理propofol可以維持menadione處裡的THP-1細胞內SOD與y-GCS的表現。另一個抗氧化酵素過氧化氫酶的表現則不會受到menadione及propofol的影響。另外在上述四種鎮靜藥物中，只有propofol可以有效減少細胞內cumene與超氧化物的濃度。
結論：我們的實驗結果顯示，在四種被測試的靜脈鎮靜劑中，Propofol是較其他藥物最具有抗氧化能力與清除活性氧物質活性的靜脈鎮靜劑。

關鍵字

Propofol ； 抗氧化劑 ； 氧化壓力 ； 靜脈鎮靜劑

並列摘要

Background: Propofol, thiopental, citosol, and midazolam are widely used as sedatives for the critically ill in the intensive care unit. These patients usually suffer from cellular injuries caused by oxidative stress from free radicals, predominantly due to the lack of a sufficient defense system against these species. Therefore, the antioxidant activities of sedative drugs may be clinically important. We attempt to evaluate the antioxidant and reactive oxygen species scavenging activities of these clinically relevant intravenous sedatives.
Methods: By using Menadione, Hydrogen peroxide and Cumene hydroperoxide to create oxidative stress in human monocyte THP-1 cell line, we evaluate the antioxidative activity of propofol, thiopental, citosol, and midazolam by means of flow cytometry to investigate the intracellular reactive oxygen species scavenging ability of these drugs in human monocyte THP-1 cell line.
Results: Propofol expressed an excellent scavenging activity compared with the other intravenous anesthetics, especially on menadione-induced superoxide in THP-1 cells. Propofol also significantly inhibits the intracellular GSH depletion and the decrease of mitochondrial transmembrane potential (△Ψ(subscript m)) induced by menadione in THP-1 cells. The expression of two antioxidant enzymes, superoxide dismutase (SOD) and gamma-glutamylcysteine synthetase (y-GCS), is inhibited by menadione treatment. Pretreatment with propofol can maintain the expression of SOD and y-GCS in menadione-treated THP-1 cells. The expression of another antioxidant enzyme, catalase, is not obviously affected by menadione and propofol.
Conclusions: Propofol, of the four drugs tested in the present study, showed the most antioxidant and reactive oxygen species scavenging activities.

並列關鍵字

Propofol ； Antioxidant ； Oxidative stress ； intravenous sedatives