{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T19:22:07Z","timestamp":1791055327150,"version":"4.1.0"},"reference-count":35,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T00:00:00Z","timestamp":1634428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005925","name":"Buddhist Tzu Chi Medical Foundation","doi-asserted-by":"publisher","award":["TCRD104-23"],"award-info":[{"award-number":["TCRD104-23"]}],"id":[{"id":"10.13039\/501100005925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST-106-2314-B-303-019-MY3"],"award-info":[{"award-number":["MOST-106-2314-B-303-019-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-\u03b1) and interleukin 1 beta (IL-1\u03b2)). In the animal model, 14-week-old conscious Wistar\u2013Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg\/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg\/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-\u03b1 and IL-1\u03b2 in conscious rats.<\/jats:p>","DOI":"10.3390\/ijms222011190","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T23:05:47Z","timestamp":1634511947000},"page":"11190","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3088-659X","authenticated-orcid":false,"given":"Tsung-Jui","family":"Wu","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Hualien Armed Forces General Hospital, Hualien 97144, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Division of Nephrology, Department of Internal medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0061-004X","authenticated-orcid":false,"given":"Yi-Jen","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wen","family":"Lu","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1418-224X","authenticated-orcid":false,"given":"Chung-Jen","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nursing, Tzu Chi University of Science and Technology, Hualien 97005, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-4558","authenticated-orcid":false,"given":"Bang-Gee","family":"Hsu","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan"},{"name":"Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/ki.2009.502","article-title":"Acute kidney injury in non-severe pneumonia is associated with an increased immune response and lower survival","volume":"77","author":"Murugan","year":"2010","journal-title":"Kidney Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.2215\/CJN.03681106","article-title":"Septic acute kidney injury in critically ill patients: Clinical characteristics and outcomes","volume":"2","author":"Bagshaw","year":"2007","journal-title":"Clin. 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