{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:28:39Z","timestamp":1792002519843,"version":"4.4.0"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Medicine &amp;amp; Sci"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI) is one of the most serious complications of sepsis, with substantial morbidity and mortality, and no effective treatment exists. Ebselen is of pharmacological significance in the treatment and prevention of a variety of human diseases, such as cancer and cardiovascular disorders. Nevertheless, the role of Ebselen in the pathogenesis of sepsis\u2010induced AKI remains unknown. Therefore, we aimed to elucidate the impact of Ebselen, an active seleno\u2010organic compound, on AKI induced by lipopolysaccharide (LPS) and the associated molecular mechanisms, including endoplasmic reticulum (ER) stress, apoptosis, and oxidative stress. We established the sepsis\u2010induced AKI rat model by injecting 5\u00a0mg\/kg of LPS intraperitoneally. The rats were given Ebselen (5 and 10\u00a0mg\/kg, orally) before receiving the LPS injection. Ebselen treatment alleviated renal tubular injury and reduced the levels of blood urea nitrogen (BUN) and creatinine (CREA) in LPS\u2010induced sepsis model. Immunohistochemical and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) analyses revealed that Ebselen reduced caspase\u20103 expressions and apoptotic cells triggered by LPS in kidney tissues. LPS\u2010induced sepsis caused ER stress, and Ebselen treatment alleviated the ER stress by regulating eukaryotic translation initiation factor 2\u2010alpha kinase 3 (EIF2AK3) and GRP78 in kidney tissue, as well as activating transcription factor 4 (ATF4) and activating transcription factor 6 (ATF6) in serum. Ebselen decreased malondialdehyde (MDA) levels induced by LPS. Ebselen alleviated LPS\u2010induced oxidative stress by modulating MDA and superoxide dismutase (SOD) levels in kidney tissues and SOD, glutathione peroxidase (GPx) and serum total antioxidant status (TAS) levels in serum. In conclusion, we report for the time that Ebselen might alleviate sepsis\u2010induced AKI through the regulation of ER stress apoptosis and oxidative stress.<\/jats:p>","DOI":"10.1002\/vms3.70318","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T08:51:04Z","timestamp":1742719864000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Ebselen Alleviates Sepsis\u2010Induced Acute Kidney Injury by Regulating Endoplasmic Reticulum Stress, Apoptosis, and Oxidative Stress"],"prefix":"10.1002","volume":"11","author":[{"given":"\u0130hsan","family":"Karabo\u011fa","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine K\u0131rklareli University  K\u0131rklareli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7616-3330","authenticated-orcid":false,"given":"Hamza Malik","family":"Okuyan","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy and Rehabilitation\u2014Faculty of Health Sciences, Biomedical Technologies Application and Research Center, Physiotherapy and Rehabilitation Application and Research Center Sakarya University of Applied Sciences  Sakarya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serdar","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine Hatay Mustafa Kemal University  Hatay T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eeyda \u00d6znur","family":"Ay\u00e7i\u00e7ek","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy and Rehabilitation\u2014Faculty of Health Sciences, Biomedical Technologies Application and Research Center, Physiotherapy and Rehabilitation Application and Research Center Sakarya University of Applied Sciences  Sakarya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3445-6060","authenticated-orcid":false,"given":"H\u00fcseyin","family":"\u00c7ak\u0131ro\u011flu","sequence":"additional","affiliation":[{"name":"Experimental Medicine Application and Research Center Sakarya University  Sakarya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2020.110932"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic201603v"},{"issue":"1","key":"e_1_2_11_4_1","first-page":"120","article-title":"Experimental Sepsis Models: Advantages and Limitations","volume":"55","author":"Aydin P.","year":"2023","journal-title":"Eurasian Journal of Medicine"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-014-3417-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11112096"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-024-06600-1"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0210"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2019.01.009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1408-5"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1099800403261350"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9030695"},{"issue":"1","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"S41","DOI":"10.1016\/j.nephro.2016.02.005","article-title":"Acute Kidney Injury and Chronic Kidney Disease: From the Laboratory to the Clinic","volume":"12","author":"Ferenbach D.","year":"2016","journal-title":"N\u00e9phrologie & Th\u00e9rapeutique"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2020.126482"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/CAD.0000000000000835"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00477.2006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1064"},{"issue":"5","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1159\/000127432","article-title":"Prolonged Endoplasmic Reticulum Stress Induces Apoptotic Cell Death in an Experimental Model of Chronic Cyclosporine Nephropathy","volume":"28","author":"Han S. 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