Login Register Cart 0
Generic placeholder image

Current Neurovascular Research

Editor-in-Chief

ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Ethyl Pyruvate Alleviating Inflammatory Response after Diabetic Cerebral Hemorrhage

Author(s): Yueying Wang, Ke Li, Zhiyi Liu, Yulan Sun, JiaJun Wang, Qi Liu, Yuejia Song* and Jiping Qi*

Volume 19, Issue 2, 2022

Published on: 05 July, 2022

Page: [196 - 202] Pages: 7

DOI: 10.2174/1567202619666220602153937

Price: $65

Abstract

Objective: This study’s purpose is to investigate the neuroprotective role of ethyl pyruvate (EP) in the pathogenesis of diabetic intracerebral hemorrhage.

Methods: The present study used a mouse model of collagenase-induced intracerebral hemorrhage (ICH) and streptozotocin-induced diabetes. The C57BL/6 mice were randomly divided into 3 groups: sham operation, diabetic cerebral hemorrhage, and diabetic cerebral hemorrhage with EP. The EP (80 mg/kg) and EP (50 mg/kg) were injected intraperitoneally one day and one hour before modeling. The protein expression levels of high mobility group box 1 (HMGB1) and NOD-like receptors 3 (NLRP3) were detected with western blot. The mRNA levels of HMGB1 and toll-like receptor 4 (TLR4) were measured by quantitative real-time polymerase chain reaction (PCR). Immunofluorescence and ELISA were performed to confirm some inflammatory factors.

Results: Compared to the normal diabetic intracerebral hemorrhage group, the mRNA and protein expression levels of HMGB1 and TLR4 were downregulated in the EP-affected group with diabetic cerebral hemorrhage, together with the downregulation of the expression of inflammasomes, including NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase 1.

Conclusion: EP can reduce the inflammatory response after diabetic intracerebral hemorrhage and may inhibit the activation of inflammasomes by the HMGB1/TLR4 pathway.

Keywords: Diabetic cerebral hemorrhage, EP, inflammasome, HMGB1, TLR4, ethyl pyruvate.

« Previous Next »
[1]
An SJ, Kim TJ, Yoon BW. Epidemiology, risk factorS, and clinical features of Intracerebral hemorrhage: An Update. J Stroke 2017; 19(1): 3-10.
[http://dx.doi.org/10.5853/jos.2016.00864] [PMID: 28178408]
[2]
McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet 2012; 379(9833): 2291-9.
[http://dx.doi.org/10.1016/S0140-6736(12)60360-2] [PMID: 22683129]
[3]
Sarwar N, Gao P, Seshasai SR, et al. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: A collaborative meta-analysis of 102 prospective studies. Lancet 2010; 375(9733): 2215-22.
[http://dx.doi.org/10.1016/S0140-6736(10)60484-9] [PMID: 20609967]
[4]
Saliba W, Barnett-Griness O, Gronich N, et al. Association of diabetes and glycated hemoglobin with the risk of intracerebral hemorrhage: A Population-Based Cohort Study. Diabetes Care 2019; 42(4): 682-8.
[http://dx.doi.org/10.2337/dc18-2472] [PMID: 30728223]
[5]
Liebkind R, Gordin D, Strbian D, et al. Diabetes and intracerebral hemorrhage: Baseline characteristics and mortality. Eur J Neurol 2018; 25(6): 825-32.
[http://dx.doi.org/10.1111/ene.13603] [PMID: 29443444]
[6]
Tetri S, Juvela S, Saloheimo P, Pyhtinen J, Hillbom M. Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage. J Neurosurg 2009; 110(3): 411-7.
[http://dx.doi.org/10.3171/2008.8.JNS08445] [PMID: 19249937]
[7]
Bierhaus A, Schiekofer S, Schwaninger M, et al. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes 2001; 50(12): 2792-808.
[http://dx.doi.org/10.2337/diabetes.50.12.2792] [PMID: 11723063]
[8]
Baldwin AS Jr. The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu Rev Immunol 1996; 14: 649-83.
[http://dx.doi.org/10.1146/annurev.immunol.14.1.649] [PMID: 8717528]
[9]
Müller M, Morotti A, Ponzetto C. Activation of NF-kappaB is essential for hepatocyte growth factor-mediated proliferation and tubulogenesis. Mol Cell Biol 2002; 22(4): 1060-72.
[http://dx.doi.org/10.1128/MCB.22.4.1060-1072.2002] [PMID: 11809798]
[10]
Kao KK, Fink MP. The biochemical basis for the anti-inflammatory and cytoprotective actions of ethyl pyruvate and related compounds. Biochem Pharmacol 2010; 80(2): 151-9.
[http://dx.doi.org/10.1016/j.bcp.2010.03.007] [PMID: 20230800]
[11]
Fink MP. Ethyl pyruvate: A novel treatment for sepsis. Curr Drug Targets 2007; 8(4): 515-8.
[http://dx.doi.org/10.2174/138945007780362791] [PMID: 17430122]
[12]
Fink MP. Ethyl pyruvate. Curr Opin Anaesthesiol 2008; 21(2): 160-7.
[http://dx.doi.org/10.1097/ACO.0b013e3282f63c2e] [PMID: 18443482]
[13]
Relja B, Omid N, Kontradowitz K, et al. Decreased inflammatory responses of human lung epithelial cells after ethanol exposure are mimicked by ethyl pyruvate. Mediators Inflamm 2014; 2014: 781519.
[http://dx.doi.org/10.1155/2014/781519] [PMID: 25530684]
[14]
Relja B, Omid N, Schaible A, et al. Pre- or post-treatment with ethanol and ethyl pyruvate results in distinct anti-inflammatory responses of human lung epithelial cells triggered by interleukin-6. Mol Med Rep 2015; 12(2): 2991-8.
[http://dx.doi.org/10.3892/mmr.2015.3764] [PMID: 25954992]
[15]
Cai B, Brunner M, Wang H, Wang P, Deitch EA, Ulloa L. Ethyl pyruvate improves survival in awake hemorrhage. J Mol Med (Berl) 2009; 87(4): 423-33.
[http://dx.doi.org/10.1007/s00109-009-0441-8] [PMID: 19172241]
[16]
Nguyen BN, Albadawi H, Oklu R, et al. Ethyl pyruvate modulates delayed paralysis following thoracic aortic ischemia reperfusion in mice. J Vasc Surg 2016; 64(5): 1433-43.
[http://dx.doi.org/10.1016/j.jvs.2015.06.214] [PMID: 27776698]
[17]
Relja B, Wagner N, Franz N, et al. Ethyl pyruvate reduces acute lung damage following trauma and hemorrhagic shock via inhibition of NF-κB and HMGB1. Immunobiology 2018; 223(3): 310-8.
[http://dx.doi.org/10.1016/j.imbio.2017.10.037] [PMID: 29102048]
[18]
Li S, Liang F, Kwan K, et al. Identification of ethyl pyruvate as a NLRP3 inflammasome inhibitor that preserves mitochondrial integrity. Mol Med 2018; 24(1): 8.
[http://dx.doi.org/10.1186/s10020-018-0006-9] [PMID: 30134814]
[19]
Lee YM, Kim J, Jo K, et al. Ethyl pyruvate inhibits retinal pathogenic neovascularization by downregulating HMGB1 expression. J Diabetes Res 2013; 2013: 245271.
[http://dx.doi.org/10.1155/2013/245271] [PMID: 24371837]
[20]
Ju KD, Shin EK, Cho EJ, et al. Ethyl pyruvate ameliorates albuminuria and glomerular injury in the animal model of diabetic nephropathy. Am J Physiol Renal Physiol 2012; 302(5): F606-13.
[http://dx.doi.org/10.1152/ajprenal.00415.2011] [PMID: 22129969]
[21]
Jovanović Stojanov S, Martinović V, Bogojević D, et al. Modulation of diabetes-related liver injury by the HMGB1/TLR4 inflammatory pathway. J Physiol Biochem 2018; 74(2): 345-58.
[http://dx.doi.org/10.1007/s13105-018-0626-0] [PMID: 29611132]
[22]
Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G. The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 2009; 10(3): 241-7.
[http://dx.doi.org/10.1038/ni.1703] [PMID: 19221555]
[23]
Paik S, Kim JK, Silwal P, Sasakawa C, Jo EK. An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol 2021; 18(5): 1141-60.
[http://dx.doi.org/10.1038/s41423-021-00670-3] [PMID: 33850310]
[24]
Frank MG, Weber MD, Watkins LR, Maier SF. Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming. Brain Behav Immun 2015; 48: 1-7.
[http://dx.doi.org/10.1016/j.bbi.2015.03.010]
[25]
Mazarati A, Maroso M, Iori V, Vezzani A, Carli M. High-mobility group box-1 impairs memory in mice through both toll-like receptor 4 and Receptor for Advanced Glycation End Products. Exp Neurol 2011; 232(2): 143-8.
[http://dx.doi.org/10.1016/j.expneurol.2011.08.012] [PMID: 21884699]
[26]
Koprivica I, Djedovic N, Stojanović I, Miljković D. Ethyl pyruvate, a versatile protector in infammation and autoimmunity. Inflammation Research, AG 2021; 71: 169-82.
[27]
Jang SE, Jeong JJ, Hyam SR, Han MJ, Kim DH. Ursolic acid isolated from the seed of Cornus officinalis ameliorates colitis in mice by inhibiting the binding of lipopolysaccharide to Toll-like receptor 4 on macrophages. J Agric Food Chem 2014; 62(40): 9711-21.
[http://dx.doi.org/10.1021/jf501487v] [PMID: 25213465]
[28]
Zhang S, Hu L, Jiang J, et al. HMGB1/RAGE axis mediates stress-induced RVLM neuroinflammation in mice via impairing mitophagy flux in microglia. J Neuroinflam 2020; 17(1): 15.
[http://dx.doi.org/10.1186/s12974-019-1673-3] [PMID: 31924219]

Rights & Permissions Print Cite
Article Metrics
10
© 2024 Bentham Science Publishers | Privacy Policy