Drug-drug Interactions Between Propofol and ART Drugs: Inhibiting Neuronal Activity by Affecting Glucose Metabolism

Overview

Journal CNS Neurosci Ther

Specialties Neurology
Pharmacology

Date 2023 Aug 31

PMID 37650345

Authors

Sijun Li

Yanqing Zheng

Qian Long

Jianhong Nong

Honghua Shao

Gang Liang

Fengyao Wu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Molecular Precision Medicine: Application of Physiologically Based Pharmacokinetic Modeling to Predict Drug-Drug Interactions Between Lidocaine and Rocuronium/Propofol/Paracetamol.

Silva A, Mourao J, Vale N Int J Mol Sci. 2025; 26(4).

PMID: 40003969 PMC: 11855824. DOI: 10.3390/ijms26041506.

NDUFA11 may be the disulfidptosis-related biomarker of ischemic stroke based on integrated bioinformatics, clinical samples, and experimental analyses.

Li S, Chen N, He J, Luo X, Lin W Front Neurosci. 2025; 18:1505493.

PMID: 39877656 PMC: 11772302. DOI: 10.3389/fnins.2024.1505493.

Exploring the Interaction of 3-Hydroxy-4-pyridinone Chelators with Liposome Membrane Models: Insights from DSC and EPR Analysis.

Amaral L, Moniz T, Rangel M Molecules. 2025; 29(24.

PMID: 39769994 PMC: 11676919. DOI: 10.3390/molecules29245905.

Association between lactate metabolism‑related molecules and venous thromboembolism: A study based on bioinformatics and an model.

Qin Z, Chen J, Zhang J, Lu H, Chen Q Exp Ther Med. 2024; 27(2):70.

PMID: 38234631 PMC: 10792409. DOI: 10.3892/etm.2023.12359.

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

Li S, Zheng Y, Long Q, Nong J, Shao H, Liang G CNS Neurosci Ther. 2023; 30(3):e14437.

PMID: 37650345 PMC: 10916437. DOI: 10.1111/cns.14437.

References

Besson M, Dupont P, Fridell Y, Lievens J . Increased energy metabolism rescues glia-induced pathology in a Drosophila model of Huntington's disease. Hum Mol Genet. 2010; 19(17):3372-82. DOI: 10.1093/hmg/ddq249. View

Li S, Zheng Y, Long Q, Nong J, Shao H, Liang G . Drug-drug interactions between propofol and ART drugs: Inhibiting neuronal activity by affecting glucose metabolism. CNS Neurosci Ther. 2023; 30(3):e14437. PMC: 10916437. DOI: 10.1111/cns.14437. View

Xia C, Luo D, Yu X, Jiang S, Liu S . HIV-associated dementia in the era of highly active antiretroviral therapy (HAART). Microbes Infect. 2011; 13(5):419-25. DOI: 10.1016/j.micinf.2011.01.004. View

Gerhart D, Broderius M, Borson N, Drewes L . Neurons and microvessels express the brain glucose transporter protein GLUT3. Proc Natl Acad Sci U S A. 1992; 89(2):733-7. PMC: 48313. DOI: 10.1073/pnas.89.2.733. View

Weber B, Keller A, Reichold J, Logothetis N . The microvascular system of the striate and extrastriate visual cortex of the macaque. Cereb Cortex. 2008; 18(10):2318-30. DOI: 10.1093/cercor/bhm259. View

Manolescu A, Augustin R, Moley K, Cheeseman C . A highly conserved hydrophobic motif in the exofacial vestibule of fructose transporting SLC2A proteins acts as a critical determinant of their substrate selectivity. Mol Membr Biol. 2007; 24(5-6):455-63. DOI: 10.1080/09687680701298143. View

Howarth C, Gleeson P, Attwell D . Updated energy budgets for neural computation in the neocortex and cerebellum. J Cereb Blood Flow Metab. 2012; 32(7):1222-32. PMC: 3390818. DOI: 10.1038/jcbfm.2012.35. View

Nakajima K, Yin X, Takei Y, Seog D, Homma N, Hirokawa N . Molecular motor KIF5A is essential for GABA(A) receptor transport, and KIF5A deletion causes epilepsy. Neuron. 2012; 76(5):945-61. DOI: 10.1016/j.neuron.2012.10.012. View

Niccoli T, Cabecinha M, Tillmann A, Kerr F, Wong C, Cardenes D . Increased Glucose Transport into Neurons Rescues Aβ Toxicity in Drosophila. Curr Biol. 2016; 26(17):2291-300. PMC: 5026704. DOI: 10.1016/j.cub.2016.07.017. View

10.

Emami S, Valipour M, Kazemi Komishani F, Sadati-Ashrafi F, Rasoulian M, Ghasemian M . Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents. Bioorg Chem. 2021; 112:104943. DOI: 10.1016/j.bioorg.2021.104943. View

11.

Andrada J, Livingston P, Lee B, Antognini J . Propofol and etomidate depress cortical, thalamic, and reticular formation neurons during anesthetic-induced unconsciousness. Anesth Analg. 2011; 114(3):661-9. DOI: 10.1213/ANE.0b013e3182405228. View

12.

Leino R, Gerhart D, van Bueren A, McCall A, Drewes L . Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain. J Neurosci Res. 1997; 49(5):617-26. DOI: 10.1002/(SICI)1097-4547(19970901)49:5<617::AID-JNR12>3.0.CO;2-S. View

13.

De Santi S, de Leon M, Rusinek H, Convit A, Tarshish C, Roche A . Hippocampal formation glucose metabolism and volume losses in MCI and AD. Neurobiol Aging. 2001; 22(4):529-39. DOI: 10.1016/s0197-4580(01)00230-5. View

14.

Brekke E, Berger H, WiderOe M, Sonnewald U, Morken T . Glucose and Intermediary Metabolism and Astrocyte-Neuron Interactions Following Neonatal Hypoxia-Ischemia in Rat. Neurochem Res. 2016; 42(1):115-132. DOI: 10.1007/s11064-016-2149-9. View

15.

Zhang S, Liu D, Wang L, Li Y, Wang Y, Zhang H . A CASPR1-ATP1B3 protein interaction modulates plasma membrane localization of Na/K-ATPase in brain microvascular endothelial cells. J Biol Chem. 2019; 294(16):6375-6386. PMC: 6484117. DOI: 10.1074/jbc.RA118.006263. View

16.

Attwell D, Laughlin S . An energy budget for signaling in the grey matter of the brain. J Cereb Blood Flow Metab. 2001; 21(10):1133-45. DOI: 10.1097/00004647-200110000-00001. View

17.

Krajcova A, Waldauf P, Andel M, Duska F . Propofol infusion syndrome: a structured review of experimental studies and 153 published case reports. Crit Care. 2015; 19:398. PMC: 4642662. DOI: 10.1186/s13054-015-1112-5. View

18.

Maher F, Davies-Hill T, Lysko P, Henneberry R, Simpson I . Expression of two glucose transporters, GLUT1 and GLUT3, in cultured cerebellar neurons: Evidence for neuron-specific expression of GLUT3. Mol Cell Neurosci. 2009; 2(4):351-60. DOI: 10.1016/1044-7431(91)90066-w. View

19.

Malaspina P, Roullet J, Pearl P, Ainslie G, Vogel K, Gibson K . Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism. Neurochem Int. 2016; 99:72-84. PMC: 5028283. DOI: 10.1016/j.neuint.2016.06.009. View

20.

Hasebe M, Shibue K, Honjo S, Hamasaki A . Hypoglycemic encephalopathy. QJM. 2022; 115(7):478-479. DOI: 10.1093/qjmed/hcac125. View