Department of Anesthesiology and Reanimation, Department of Medicinal Biochemistry, Department of Biostatistics, Faculty of Medicine, Harran University, Sanliurfa, Turkey.
Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1336-1345. doi: 10.26355/eurrev_202302_31367.
Propofol, thiopental and dexmedetomidine are hypnotic, sedative, antiepileptic and analgesic agents used in general anesthesia and intensive care. There are many known and yet unknown side effects. Our aim in this study was to examine and compare the cytotoxic, reactive oxygen species (ROS) and apoptotic effects of propofol, thiopental and dexmedetomidine drugs, which are widely used in anesthesia, on liver cells (AML12) in vitro.
The half-maximum inhibitory concentration (IC50) doses of the three drugs on AML12 cells were determined using the 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) method. Then at two different doses of each of the three drugs, apoptotic effects were determined by the Annexin-V method, morphological examinations were determined by acridine orange ethidium bromide method and intracellular reactive oxygen species (ROS) levels were determined by flow cytometry.
The IC50 thiopental, propofol and dexmedetomidine doses were found to be 255.008, 254.904 and 34.501 μgr/mL, respectively (p<0.001). The highest cytotoxic effect on liver cells was found in the lowest dose of dexmedetomidine (34.501 μgr/mL) compared to the control group. This was followed by thiopental and propofol, respectively.
In this study, propofol, thiopental and dexmedetomidine drugs on AML12 cells were found to have toxic effects by increasing intracellular ROS at two different concentrations higher than clinical doses. It was determined that cytotoxic doses caused an increase in ROS and induced apoptosis in cells. We believe that the toxic effects of these drugs can be prevented by examining the values obtained from this study and the results of future studies.
丙泊酚、硫喷妥钠和右美托咪定是在全身麻醉和重症监护中使用的催眠、镇静、抗癫痫和镇痛剂。它们有许多已知和未知的副作用。我们在这项研究中的目的是检查和比较丙泊酚、硫喷妥钠和右美托咪定这三种在麻醉中广泛使用的药物对体外肝细胞（AML12）的细胞毒性、活性氧（ROS）和凋亡作用。
使用 3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴化物（MTT）法测定三种药物对 AML12 细胞的半最大抑制浓度（IC50）剂量。然后，在三种药物的两种不同剂量下，通过 Annexin-V 法测定凋亡作用，通过吖啶橙溴化乙锭法测定形态学检查，通过流式细胞术测定细胞内活性氧（ROS）水平。
发现硫喷妥钠、丙泊酚和右美托咪定的 IC50 剂量分别为 255.008、254.904 和 34.501 μg/mL（p<0.001）。与对照组相比，在最低剂量的右美托咪定（34.501 μg/mL）下，对肝细胞的细胞毒性作用最大。其次是硫喷妥钠和丙泊酚。
在这项研究中，发现丙泊酚、硫喷妥钠和右美托咪定三种药物在两种高于临床剂量的不同浓度下通过增加细胞内 ROS 对 AML12 细胞具有毒性作用。确定细胞毒性剂量会导致 ROS 增加，并诱导细胞凋亡。我们相信，通过检查从这项研究获得的值和未来研究的结果，可以预防这些药物的毒性作用。
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