{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T17:30:34Z","timestamp":1775496634038,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81971881"],"award-info":[{"award-number":["No. 81971881"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Surg."],"abstract":"<jats:p>Brain death (BD) induces an organ-level inflammatory response. However, the underlying mechanisms have not been fully elucidated. Here, we investigated the role of caspase-1-mediated pyroptosis in BD-induced kidney injury in rats. A BD model was established in Sprague-Dawley rats. The rats were intravenously injected with Z-YVAD-FMK 1 h before BD, and sham-operated rats served as controls. After 0, 1, 2, 4, and 6 h of BD, renal injury, and renal expression of the nod-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, caspase-11, gasdermin D (GSDMD), IL-1\u03b2, and IL-18 were assessed using quantitative reverse transcriptase-polymerase chain reaction, western blotting, and immunohistochemistry. Blood urea nitrogen and serum creatinine levels were measured. Additionally, renal tubular epithelial cells (NRK-52E) were subjected to 3 h of hypoxia followed by 6 h of reoxygenation and incubated with Z-YVAD-FMK before hypoxia and reoxygenation. Caspase-11 was knocked-down using small interfering RNA technology. Cell viability and levels of pyroptosis-associated proteins were assessed thereafter. NLRP3, caspase-1, GSDMD, IL-1\u03b2, and IL-18 expression levels were upregulated in BD rats. Treatment with Z-YVAD-FMK reduced mRNA and protein levels of caspase-1, GSDMD, IL-1\u03b2, and IL-18, improved renal function, and alleviated renal injury. Z-YVAD-FMK efficaciously reduced pyroptosis effects in kidneys in BD rats. Thus, it could be considered as a therapeutic target for BD-induced kidney injury.<\/jats:p>","DOI":"10.3389\/fsurg.2021.760989","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T08:02:19Z","timestamp":1638345739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Caspase-1 Inhibitor Reduces Pyroptosis Induced by Brain Death in Kidney"],"prefix":"10.3389","volume":"8","author":[{"given":"Weifeng","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongjing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peihao","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiakai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bowen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyi","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shengli","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuijun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1111\/j.1399-6576.2008.01879.x","article-title":"Systemic inflammation in the brain-dead organ donor","volume":"53","author":"HBarklin","year":"2009","journal-title":"Acta Anaesthesiol Scand."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1097\/TP.0000000000002744","article-title":"Brain death enhances activation of the innate immune system and leads to reduced renal metabolic gene expression","volume":"103","author":"Zitur","year":"2019","journal-title":"Transplantation."},{"key":"B3","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1056\/NEJM200003023420901","article-title":"Improved graft survival after renal transplantation in the United States, 1988 to 1996","volume":"342","author":"Hariharan","year":"2000","journal-title":"N Engl J Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1111\/ajt.13144","article-title":"Associations of deceased donor kidney injury with kidney discard and function after transplantation","volume":"15","author":"Hall","year":"2015","journal-title":"Am J Transplant."},{"key":"B5","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1161\/01.CIR.102.3.326","article-title":"Tumor necrosis factor-alpha is expressed in donor heart and predicts right ventricular failure after human heart transplantation","volume":"102","author":"Birks","year":"2000","journal-title":"Circulation."},{"key":"B6","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1097\/01.TP.0000135565.49535.60","article-title":"Effect of brain death on gene expression and tissue activation in human donor kidneys","volume":"78","author":"Nijboer","year":"2004","journal-title":"Transplantation."},{"key":"B7","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1038\/ki.2011.120","article-title":"Apoptosis and acute kidney injury","volume":"80","author":"Havasi","year":"2011","journal-title":"Kidney Int."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1681\/ASN.2014030262","article-title":"Regulated cell death in AKI","volume":"25","author":"Linkermann","year":"2014","journal-title":"J Am Soc Nephrol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3598","DOI":"10.3390\/ijms20143598","article-title":"Cell death in the kidney","volume":"20","author":"Priante","year":"2019","journal-title":"Int J Mol Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1111\/imr.12534","article-title":"Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases","volume":"277","author":"Man","year":"2017","journal-title":"Immunol Rev."},{"key":"B11","doi-asserted-by":"publisher","first-page":"R568","DOI":"10.1016\/j.cub.2016.02.019","article-title":"Pyroptosis","volume":"26","author":"Vande Walle","year":"2016","journal-title":"Curr Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.brainres.2018.06.008","article-title":"The pathological role of NLRs and AIM2 inflammasome-mediated pyroptosis in damaged blood-brain barrier after traumatic brain injury","volume":"1697","author":"Ge","year":"2018","journal-title":"Brain Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"e790","DOI":"10.1038\/cddis.2013.326","article-title":"Intravenous immunoglobulin suppresses NLRP1 and NLRP3 inflammasome-mediated neuronal death in ischemic stroke","volume":"4","author":"Fann","year":"2013","journal-title":"Cell Death Dis."},{"key":"B14","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.tcb.2017.05.005","article-title":"Gasdermins: effectors of pyroptosis","volume":"27","author":"Kovacs","year":"2017","journal-title":"Trends Cell Biol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12974-018-1083-y","article-title":"Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo","volume":"15","author":"Liu","year":"2018","journal-title":"J Neuroinflammation."},{"key":"B16","doi-asserted-by":"publisher","first-page":"5160","DOI":"10.1002\/jcp.26287","article-title":"Inflammasome: its role in traumatic brain and spinal cord injury","volume":"233","author":"Mortezaee","year":"2018","journal-title":"J Cell Physiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"F75","DOI":"10.1152\/ajprenal.00117.2013","article-title":"Ischemia-reperfusion induces renal tubule pyroptosis via the CHOP-caspase-11 pathway","volume":"306","author":"Yang","year":"2014","journal-title":"Am J Physiol Renal Physiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.urology.2018.10.015","article-title":"Combined ischemic postconditioning and ozone postconditioning provides synergistic protection against renal ischemia and reperfusion injury through inhibiting pyroptosis","volume":"123","author":"Wang","year":"2019","journal-title":"Urology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1111\/jcmm.12676","article-title":"Myocardial protective effects of a c-Jun N-terminal kinase inhibitor in rats with brain death","volume":"20","author":"Guo","year":"2016","journal-title":"J Cell Mol Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ecoenv.2019.02.069","article-title":"Inhibition of caspase-1-dependent pyroptosis attenuates copper-induced apoptosis in chicken hepatocytes","volume":"174","author":"Liao","year":"2019","journal-title":"Ecotoxicol Environ Saf."},{"key":"B21","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1002\/jnr.24385","article-title":"Gasdermin D serves as a key executioner of pyroptosis in experimental cerebral ischemia and reperfusion model both in vivo and in vitro","volume":"97","author":"Zhang","year":"2019","journal-title":"J Neurosci Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1097\/00007890-200002150-00020","article-title":"A model of gradual onset brain death for transplant-associated studies in rats","volume":"69","author":"Pratschke","year":"2000","journal-title":"Transplantation."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1038\/ki.1991.312","article-title":"Reactive oxygen species and rat renal epithelial cells during hypoxia and reoxygenation","volume":"40","author":"Paller","year":"1991","journal-title":"Kidney Int."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4637","DOI":"10.7150\/thno.56082","article-title":"Relieving lipid accumulation through UCP1 suppresses the progression of acute kidney injury by promoting the AMPK\/ULK1\/autophagy pathway","volume":"11","author":"Xiong","year":"2021","journal-title":"Theranostics."},{"key":"B25","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.bbrc.2021.03.048","article-title":"Effects of chitinase-3-like protein 1 on brain death-induced hepatocyte apoptosis via PAR2-JNK-caspase-3","volume":"552","author":"Li","year":"2021","journal-title":"Biochem Biophys Res Commun."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/5604843","article-title":"Microarray analysis for expression profiles of lncRNAs and circRNAs in rat liver after brain-dead donor liver transplantation","volume":"2019","author":"Chen","year":"2019","journal-title":"Biomed Res Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1055\/s-2007-1011985","article-title":"Hemodynamic and metabolic disturbances observed in brain-dead organ donors","volume":"28","author":"Lagiewska","year":"1996","journal-title":"Transplant Proc."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1038\/ki.1993.192","article-title":"Clinicopathology of kidneys from brain-dead patients treated with vasopressin and epinephrine","volume":"43","author":"Nagareda","year":"1993","journal-title":"Kidney Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/S1053-2498(00)00073-5","article-title":"Brain death and its impact on the donor heart-lessons from animal models","volume":"19","author":"Wilhelm","year":"2000","journal-title":"J Heart Lung Transplant."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1097\/00007890-199806270-00001","article-title":"Effects of explosive brain death on cytokine activation of peripheral organs in the rat","volume":"65","author":"Takada","year":"1998","journal-title":"Transplantation."},{"key":"B31","first-page":"725","article-title":"Apoptosis of rat renal cells by organophosphate pesticide, quinalphos: ultrastructural study","volume":"28","author":"Eid","year":"2017","journal-title":"Saudi J Kidney Dis Transpl."},{"key":"B32","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1093\/ckj\/sfx062","article-title":"Environmental toxin-induced acute kidney injury","volume":"10","author":"Vervaet","year":"2017","journal-title":"Clin Kidney J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1038\/nature10558","article-title":"Non-canonical inflammasome activation targets caspase-11","volume":"479","author":"Kayagaki","year":"2011","journal-title":"Nature."},{"key":"B34","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/S0092-8674(00)80943-5","article-title":"Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE","volume":"92","author":"Wang","year":"1998","journal-title":"Cell."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.3390\/ijms17091418","article-title":"Ruscogenin attenuates cerebral ischemia-induced blood-brain barrier dysfunction by suppressing TXNIP\/NLRP3 inflammasome activation and the MAPK pathway","volume":"17","author":"Cao","year":"2016","journal-title":"Int J Mol Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1007\/s11033-019-04674-1","article-title":"Renal effects of exendin-4 in an animal model of brain death","volume":"46","author":"Lemos","year":"2019","journal-title":"Mol Biol Rep."},{"key":"B37","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.rvsc.2019.02.004","article-title":"Pyroptosis is involved in cryopreservation and auto-transplantation of mouse ovarian tissues and pyroptosis inhibition improves ovarian graft function","volume":"124","author":"Wang","year":"2019","journal-title":"Res Vet Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"a036392","DOI":"10.1101\/cshperspect.a036392","article-title":"Recent insights on inflammasomes, gasdermin pores, and pyroptosis","volume":"12","author":"de Vasconcelos","year":"2020","journal-title":"Cold Spring Harb Perspect Biol."}],"container-title":["Frontiers in Surgery"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2021.760989\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T08:02:23Z","timestamp":1638345743000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fsurg.2021.760989\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,26]]},"references-count":38,"alternative-id":["10.3389\/fsurg.2021.760989"],"URL":"https:\/\/doi.org\/10.3389\/fsurg.2021.760989","relation":{},"ISSN":["2296-875X"],"issn-type":[{"value":"2296-875X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,26]]},"article-number":"760989"}}