Drug–drug interactions between propofol and ART drugs: Inhibiting neuronal activity by affecting glucose metabolism

• Published in: CNS neuroscience & therapeutics 2024-03, Vol.30 (3), p.e14437-n/a
• Main Authors: Li, Sijun, Zheng, Yanqing, Long, Qian, Nong, Jianhong, Shao, Honghua, Liang, Gang, Wu, Fengyao
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Action potential; AIDS; Anesthesia; Animal cognition; Antibodies; Antiretroviral therapy; ART drugs; Cell membranes; Cognitive ability; Drug interaction; Drug interactions; Drug metabolism; Electrophysiology; Energy metabolism; Glucose; Glucose metabolism; Glucose transporter; glucose transporter 3; HIV; Human immunodeficiency virus; Medical research; Metabolic disorders; neuron; Neurons; Original; Propofol; Proteins; Side effects; Software; Statistical analysis; Zidovudine
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.14437

Background The use of two or more drugs carries the potential risk of drug–drug interactions (DDIs), which may result in adverse reactions. Some human immunodeficiency virus (HIV)‐infected patients who receive antiretroviral therapy (ART) may require general anesthesia with propofol (PRL) before undergoing surgical treatment. Both PRL and ART drugs may lead to neuronal dysfunction, which can be accompanied by energy metabolism disorders. Neurons take in glucose mainly through glucose transporter 3 (Glut3) which is specifically expressed on the cell membranes of neurons. However, to date, no study has examined whether the DDIs of PRL and ART drugs interfere with glucose metabolism and Glut3 expression in neurons. Methods An in vitro model was constructed using the primary cultures of neurons. PRL and ART drugs (EFV, AZT, and 3TC), were added at different concentrations (low, medium, and high). The neurons were exposed to the drugs for 1, 4, 8, and 12 h. The optimal drug concentration and exposure time were selected. The cellular survival rate, glucose concentration, electrophysiology, and the expression of Glut3 were detected. Results There were no significant changes in the cellular survival rates of the neurons that were exposed to both PRL and ART drugs at low concentrations for 1 h. However, the survival rates of the neurons decreased significantly as the drug concentrations and durations increased. The glucose concentration of the neurons that were exposed to both PRL and the ART drugs was significantly decreased. The glucose concentration of the neurons was not affected by any individual drug. The amplitude of the action potential and the expression of Glut3 were decreased in the neurons that were exposed to both PRL and ART drugs. Conclusions The main adverse reactions induced by the DDIs between PRL and the ART drugs were decreased glucose metabolism and neuronal damage, which were caused by inhibiting the expression of Glut3. More importantly, we found that decreases in glucose metabolism predated neuronal damage. The main adverse reactions induced by the drug–drug interactions between propofol (PRL) and the antiretroviral therapy (ART) drugs were decreased glucose metabolism and neuronal damage, which were caused by inhibiting the expression of glucose transporter 3.