Serum GPX4 and LPO as Biomarkers for Perioperative Oxidative Stress: Impact of Ciprofol Anesthesia in A Randomized Controlled Trial.

Background: Perioperative oxidative stress contributes to postoperative organ dysfunction, but sensitive mechanistic biomarkers are limited. Objectives: This study uses serum GPX4 and lipid peroxides to quantify oxidative stress, explore ferroptosis-related pathways, and evaluate the antioxidative effects of ciprofol anesthesia in patients undergoing thoracoscopic lung cancer surgery. Materials and Methods: Patients scheduled for video-assisted thoracoscopic surgery (VATS) for lung cancer at the Fourth Affiliated Hospital of Soochow University were enrolled and randomly assigned to one of three groups (n=50 per group): a Ciprofol group, a Propofol group, and a Sevoflurane group. The Ciprofol group received Ciprofol for induction and continuous intravenous maintenance; the Propofol group received Propofol for both induction and maintenance; and the Sevoflurane group received Ciprofol for induction followed by Sevoflurane inhalation for maintenance. Arterial blood samples were collected at four time points: before anesthesia induction (T0), after induction (T1), at the end of surgery (T2), and 24 hours postoperatively (T3). Serum levels of GPX4 and LPO were measured. Hemodynamic changes were compared among the three groups under the different anesthetic regimens. A549 lung adenocarcinoma cells were treated with varying concentrations of Ciprofol (10 µM, 25 µM, 50 µM and 100 µM) for 24 hours. Cell viability was assessed using the CCK-8 assay, and cell proliferation was evaluated using the EdU assay. After treatment, RNA was extracted from the treated and control groups for qRT-PCR analysis to measure GPX4 expression levels as an indicator of oxidative stress. Results: In the Ciprofol group, serum GPX4 levels significantly increased, while LPO levels markedly decreased at T2 and T3. In the Propofol group, GPX4 levels were significantly higher and LPO levels significantly lower at T2 and T3 compared to the Sevoflurane group (P<0.01). At T1, the heart rate in the Propofol group was significantly higher than in the Ciprofol group. At T2, heart rates in both the Propofol and Sevoflurane groups were higher than in the Ciprofol group (all P<0.01). Ciprofol treatment at 100 µM significantly inhibited tumor cell growth, with the strongest effect observed at this concentration. The subsequent experiments were conducted at 50 µM. After 24 hours, a significant decrease in GPX4 expression was observed in the treated group compared to the control group. Additionally, Ciprofol significantly inhibited tumor cell proliferation, as shown by a marked reduction in EdU-positive cells. Conclusion: Ciprofol elevates postoperative serum GPX4 and reduces LPO, alleviating oxidative stress in thoracoscopic lung cancer surgery with minimal effects on heart rate. Monitoring GPX4 and LPO may assess perioperative oxidative stress. In A549 lung adenocarcinoma cells, Ciprofol suppresses GPX4 expression and tumor proliferation, suggesting dual roles in oxidative stress modulation and tumor growth inhibition.