Comparing the Effects of Propofol and Thiopental on Human Renal HEK-293 Cells With a Focus on Reactive Oxygen Species (ROS) Production, Cytotoxicity, and Apoptosis: Insights Into Dose-Dependent Toxicity.

OBJECTIVES

Propofol and thiopental are widely used as hypnotic, sedative, antiepileptic, and analgesic agents in general anesthesia and intensive care; however, their side effects remain unknown. They are used for long periods and at high doses for sedation in total intravenous anesthesia (TIVA) and intensive care units. Long-term and high-dose use of these drugs can lead to accumulation in plasma and tissues, resulting in high drug concentrations and increasing the risk of potential toxicity (e.g., nephrotoxicity). In our study, the cytotoxic and apoptotic effects of propofol and thiopental on kidney cells (HEK-293) and their effects on the formation of reactive oxygen species (ROS) when used in high doses were investigated and compared in vitro.

MATERIALS AND METHODS

The half-maximal inhibitory concentration (IC) of each drug in HEK-293 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The apoptotic effects were assessed at two different doses of each drug using the annexin V method. Morphological examinations were conducted using the acridine orange/ethidium bromide method, and intracellular ROS levels were determined by flow cytometry.

RESULTS

The IC values of propofol and thiopental for HEK-293 cells were 206.59 μg/ml and 109.68 μg/ml, respectively. Compared to the control group, thiopental at ≥25 μg/ml and propofol at ≥50 μg/ml exhibited cytotoxicity. Additionally, propofol exhibited significantly lower cytotoxic effects than thiopental did.

CONCLUSION

Our study showed that both propofol and thiopental exerted significant cytotoxic effects on HEK-293 cells at concentrations exceeding clinical levels, primarily by increasing intracellular ROS levels and inducing apoptosis. Future research in this area will deepen our understanding of these mechanisms and improve patient safety in clinical anesthesia practice.