Comparison of cytotoxic, reactive oxygen species (ROS) and apoptotic effects of propofol, thiopental and dexmedetomidine on liver cells at accumulative doses (AML12).

Abstract

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.