Propofol and Dexmedetomidine Ameliorate Endotoxemia-Associated Encephalopathy via Inhibiting Ferroptosis

References

• Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287
   PubMed Web of Science ®Google Scholar
• Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or propofol for sedation in mechanically ventilated adults with sepsis. N Engl J Med. 2021;384(15):1424–1436. doi:10.1056/NEJMoa2024922
   PubMed Web of Science ®Google Scholar
• van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity. 2021;54(11):2450–2464. doi:10.1016/j.immuni.2021.10.012
   PubMed Web of Science ®Google Scholar
• Rajendrakumar SK, Revuri V, Samidurai M, et al. Peroxidase-mimicking nanoassembly mitigates lipopolysaccharide-induced endotoxemia and cognitive damage in the brain by impeding inflammatory signaling in macrophages. Nano Lett. 2018;18(10):6417–6426. doi:10.1021/acs.nanolett.8b02785
   PubMed Web of Science ®Google Scholar
• Xin Y, Tian M, Deng S, et al. The key drivers of brain injury by systemic inflammatory responses after sepsis: microglia and neuroinflammation. Molecular Neurobiology. 2022;60(3):1369–1390. doi:10.1007/s12035-022-03148-z
   PubMed Web of Science ®Google Scholar
• Dickson K, Lehmann C. Inflammatory response to different toxins in experimental sepsis models. Int J Mol Sci. 2019;20(18):4341. doi:10.3390/ijms20184341
   PubMed Web of Science ®Google Scholar
• Chen X, Li J, Kang R, Klionsky DJ, Tang D. Ferroptosis: machinery and regulation. Autophagy. 2021;17(9):2054–2081. doi:10.1080/15548627.2020.1810918
   PubMed Web of Science ®Google Scholar
• Tang D, Chen X, Kang R, Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31(2):107–125. doi:10.1038/s41422-020-00441-1
   PubMed Web of Science ®Google Scholar
• Yang K, Zeng L, Yuan X, et al. The mechanism of ferroptosis regulating oxidative stress in ischemic stroke and the regulation mechanism of natural pharmacological active components. Biomed Pharmacother. 2022;154:113611. doi:10.1016/j.biopha.2022.113611
   PubMed Web of Science ®Google Scholar
• Fang J, Kong B, Shuai W, et al. Ferroportin-mediated ferroptosis involved in new-onset atrial fibrillation with LPS-induced endotoxemia. Eur J Pharmacol. 2021;913:174622. doi:10.1016/j.ejphar.2021.174622
   PubMed Web of Science ®Google Scholar
• Wang X, Simayi A, Fu J, Zhao X, Xu G. Resveratrol mediates the miR-149/HMGB1 axis and regulates the ferroptosis pathway to protect myocardium in endotoxemia mice. Am J Physiol Endocrinol Metab. 2022;323(1):E21–E32. doi:10.1152/ajpendo.00227.2021
   PubMed Web of Science ®Google Scholar
• Li S, Lei Z, Yang X, et al. Propofol protects myocardium from ischemia/reperfusion injury by inhibiting ferroptosis through the AKT/p53 signaling pathway. Front Pharmacol. 2022;13:841410. doi:10.3389/fphar.2022.841410
   PubMed Web of Science ®Google Scholar
• Wei Q, Chen J, Xiao F, Tu Y, Zhong Y, Xie Y. High-dose dexmedetomidine promotes apoptosis in fetal rat hippocampal neurons. Drug Des Devel Ther. 2021;15:2433–2444. doi:10.2147/DDDT.S300247
   PubMed Web of Science ®Google Scholar
• Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825–e873. doi:10.1097/CCM.0000000000003299
   PubMed Web of Science ®Google Scholar
• Heybati K, Zhou F, Ali S, et al. Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials. Br J Anaesth. 2022;129(4):515–526. doi:10.1016/j.bja.2022.06.020
   PubMed Web of Science ®Google Scholar
• Brown EN, Pavone KJ, Naranjo M. Multimodal General Anesthesia: theory and Practice. Anesth Analg. 2018;127(5):1246–1258. doi:10.1213/ANE.0000000000003668
   PubMed Web of Science ®Google Scholar
• Tang CL, Li J, Zhang ZT, et al. Neuroprotective effect of bispectral index-guided fast-track anesthesia using sevoflurane combined with dexmedetomidine for intracranial aneurysm embolization. Neural Regen Res. 2018;13(2):280–288. doi:10.4103/1673-5374.226399
   PubMed Web of Science ®Google Scholar
• Shehabi Y, Serpa Neto A, Bellomo R, et al. Dexmedetomidine and propofol sedation in critically Ill patients and dose-associated 90-day mortality: a secondary cohort analysis of a randomized controlled trial (SPICE III). Am J Respir Crit Care Med. 2023;207(7):876–886. doi:10.1164/rccm.202206-1208OC
   PubMed Web of Science ®Google Scholar
• Shehabi Y, Howe BD, Bellomo R, et al. Early sedation with dexmedetomidine in Critically Ill Patients. N Engl J Med. 2019;380(26):2506–2517. doi:10.1056/NEJMoa1904710
   PubMed Web of Science ®Google Scholar
• Sun C, Liu P, Pei L, Zhao M, Huang Y. Propofol inhibits proliferation and augments the anti-tumor effect of doxorubicin and paclitaxel partly through promoting ferroptosis in triple-negative breast cancer cells. Front Oncol. 2022;12:837974. doi:10.3389/fonc.2022.837974
   PubMed Web of Science ®Google Scholar
• She H, Hu Y, Zhou Y, et al. Protective effects of dexmedetomidine on sepsis-induced vascular leakage by alleviating ferroptosis via regulating metabolic reprogramming. J Inflamm Res. 2021;14:6765–6782. doi:10.2147/JIR.S340420
   PubMed Web of Science ®Google Scholar
• Mei B, Li J, Zuo Z. Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central alpha2A adrenoceptor. Brain Behav Immun. 2021;91:296–314. doi:10.1016/j.bbi.2020.10.008
   PubMed Web of Science ®Google Scholar
• Guo F, Kang J, Tan J, Wang Y, Jia L, Xu H. Dexmedetomidine pretreatment improves lipopolysaccharide-induced iron homeostasis disorder in aged mice. Curr Neurovasc Res. 2020;17(2):164–170. doi:10.2174/1567202617666200217105109
   PubMed Web of Science ®Google Scholar
• Seemann S, Zohles F, Lupp A. Comprehensive comparison of three different animal models for systemic inflammation. J Biomed Sci. 2017;24(1). doi:10.1186/s12929-017-0370-8
   PubMedGoogle Scholar
• Feng H, Schorpp K, Jin J, et al. Transferrin receptor is a specific ferroptosis marker. Cell Rep. 2020;30(10):3411–3423 e7. doi:10.1016/j.celrep.2020.02.049
   PubMed Web of Science ®Google Scholar
• Moore JPR, Shehabi Y, Reade MC, et al. Stress response during early sedation with dexmedetomidine compared with usual-care in ventilated critically ill patients. Crit Care. 2022;26(1):359. doi:10.1186/s13054-022-04237-0
   PubMed Web of Science ®Google Scholar
• Hurtado-Navarro L, García-Palenciano C, Pelegrín P. Inflammasomes in sepsis. Inflammasome Biology. 2023;2023:369–382.
   Google Scholar
• Marques A, Torre C, Pinto R, Sepodes B, Rocha J. Treatment advances in sepsis and septic shock: modulating pro- and anti-inflammatory mechanisms. J Clin Med. 2023;12:8.
   Web of Science ®Google Scholar
• Ferlini L, Gaspard N. What’s new on septic encephalopathy? Ten things you need to know. Minerva Anestesiol. 2023;89(3):217–225. doi:10.23736/S0375-9393.22.16689-7
   PubMed Web of Science ®Google Scholar
• Huang X, Ye C, Zhao X, et al. TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy. J Neuroinflammation. 2023;20(1):284. doi:10.1186/s12974-023-02959-8
   PubMed Web of Science ®Google Scholar
• Liu K, Wan G, Jiang R, et al. Astragalus injection ameliorates lipopolysaccharide-induced cognitive decline via relieving acute neuroinflammation and BBB damage and upregulating the BDNF-CREB pathway in mice. Pharm Biol. 2022;60(1):825–839. doi:10.1080/13880209.2022.2062005
   PubMed Web of Science ®Google Scholar
• Xue W, Li Y, Zhang M. Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K/Akt signalling. Pharm Biol. 2021;59(1):1351–1358. doi:10.1080/13880209.2021.1981399
   PubMed Web of Science ®Google Scholar
• Wang K, Sun M, Juan Z, et al. The Improvement of Sepsis-Associated Encephalopathy by P2X7R Inhibitor through Inhibiting the Omi/HtrA2 apoptotic signaling pathway. Behav Neurol. 2022;2022:3777351. doi:10.1155/2022/3777351
   PubMed Web of Science ®Google Scholar
• Han YG, Qin X, Zhang T, et al. Electroacupuncture prevents cognitive impairment induced by lipopolysaccharide via inhibition of oxidative stress and neuroinflammation. Neurosci Lett. 2018;683:190–195. doi:10.1016/j.neulet.2018.06.003
   PubMed Web of Science ®Google Scholar
• Li Y, Ma J, Diao J, Chen W, Wang Z. Esmolol inhibits cognitive impairment and neuronal inflammation in mice with sepsis-induced brain injury. Transl Neurosci. 2023;14(1):20220297. doi:10.1515/tnsci-2022-0297
   PubMed Web of Science ®Google Scholar
• Huang M, Cai S, Su J. The pathogenesis of sepsis and potential therapeutic targets. Int J Mol Sci. 2019;20:21.
   Google Scholar
• Huo L, Liu C, Yuan Y, Liu X, Cao Q. Pharmacological inhibition of ferroptosis as a therapeutic target for sepsis-associated organ damage. Eur J Med Chem. 2023;257:115438. doi:10.1016/j.ejmech.2023.115438
   PubMed Web of Science ®Google Scholar
• Qian ZM, Ke Y. Brain iron transport. Biol Rev Camb Philos Soc. 2019;94(5):1672–1684. doi:10.1111/brv.12521
   PubMed Web of Science ®Google Scholar
• Urrutia P, Aguirre P, Esparza A, et al. Inflammation alters the expression of DMT1, FPN1 and hepcidin, and it causes iron accumulation in central nervous system cells. J Neurochem. 2013;126(4):541–549. doi:10.1111/jnc.12244
   PubMed Web of Science ®Google Scholar
• Wang J, Zhu Q, Li R, Zhang J, Ye X, Li X. YAP1 protects against septic liver injury via ferroptosis resistance. Cell Biosci. 2022;12(1):163. doi:10.1186/s13578-022-00902-7
   PubMed Web of Science ®Google Scholar
• Zhang J, Zheng Y, Wang Y, et al. YAP1 alleviates sepsis-induced acute lung injury via inhibiting ferritinophagy-mediated ferroptosis. Front Immunol. 2022;13:884362. doi:10.3389/fimmu.2022.884362
   PubMed Web of Science ®Google Scholar
• Li N, Wang W, Zhou H, et al. Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury. Free Radic Biol Med. 2020;160:303–318. doi:10.1016/j.freeradbiomed.2020.08.009
   PubMed Web of Science ®Google Scholar
• Chen Z, Cao Z, Gui F, et al. TMEM43 protects against sepsis-induced cardiac injury via inhibiting ferroptosis in mice. Cells. 2022;11:19.
   Web of Science ®Google Scholar
• Zhou B, Zhang J, Chen Y, et al. Puerarin protects against sepsis-induced myocardial injury through AMPK-mediated ferroptosis signaling. Aging. 2022;14(8):3617–3632. doi:10.18632/aging.204033
   PubMedGoogle Scholar
• Xiao Z, Kong B, Fang J, et al. Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction. Bioengineered. 2021;12(2):9367–9376. doi:10.1080/21655979.2021.2001913
   PubMed Web of Science ®Google Scholar
• Li J, Li M, Li L, Ma J, Yao C, Yao S. Hydrogen sulfide attenuates ferroptosis and stimulates autophagy by blocking mTOR signaling in sepsis-induced acute lung injury. Mol Immunol. 2022;141:318–327. doi:10.1016/j.molimm.2021.12.003
   PubMed Web of Science ®Google Scholar
• Guo J, Wang R, Min F. Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells. J Leukoc Biol. 2022;112(5):1065–1077. doi:10.1002/JLB.1A0422-211R
   PubMed Web of Science ®Google Scholar
• Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol. 2019;23:101107. doi:10.1016/j.redox.2019.101107
   PubMed Web of Science ®Google Scholar
• Kerins MJ, Ooi A. The Roles of NRF2 in modulating cellular iron homeostasis. Antioxid Redox Signal. 2018;29(17):1756–1773. doi:10.1089/ars.2017.7176
   PubMed Web of Science ®Google Scholar
• Galy B, Conrad M, Muckenthaler M. Mechanisms controlling cellular and systemic iron homeostasis. Nat Rev Mol Cell Biol. 2023;25:1. doi:10.1038/s41580-023-00648-1.
   Web of Science ®Google Scholar
• Han K, Jin X, Guo X, et al. Nrf2 knockout altered brain iron deposition and mitigated age-related motor dysfunction in aging mice. Free Radic Biol Med. 2021;162:592–602. doi:10.1016/j.freeradbiomed.2020.11.019
   PubMed Web of Science ®Google Scholar
• Li M, Zhang J, Jiang L, et al. Neuroprotective effects of morroniside from Cornus officinalis sieb. Et zucc against Parkinson’s disease via inhibiting oxidative stress and ferroptosis. BMC Complement Med Ther. 2023;23(1):218. doi:10.1186/s12906-023-03967-0
   PubMedGoogle Scholar
• Olinder J, Borjesson A, Norrman J, et al. Hepcidin discriminates sepsis from other critical illness at admission to intensive care. Sci Rep. 2022;12(1):14857. doi:10.1038/s41598-022-18826-0
   PubMed Web of Science ®Google Scholar
• Scindia Y, Wlazlo E, Leeds J, et al. protective role of hepcidin in polymicrobial sepsis and acute kidney injury. Front Pharmacol. 2019;10:615. doi:10.3389/fphar.2019.00615
   PubMed Web of Science ®Google Scholar
• You LH, Yan CZ, Zheng BJ, et al. Astrocyte hepcidin is a key factor in LPS-induced neuronal apoptosis. Cell Death Dis. 2017;8(3):e2676. doi:10.1038/cddis.2017.93
   PubMedGoogle Scholar
• Camaschella C, Nai A, Silvestri L. Iron metabolism and iron disorders revisited in the hepcidin era. Haematologica. 2020;105(2):260–272. doi:10.3324/haematol.2019.232124
   PubMed Web of Science ®Google Scholar
• Peng Y, Chang X, Lang M. Iron homeostasis disorder and alzheimer’s disease. Int J Mol Sci. 2021;22(22):12442. doi:10.3390/ijms222212442
   PubMed Web of Science ®Google Scholar