{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:56:30Z","timestamp":1774544190063,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Science, ICT and Future Planning","doi-asserted-by":"publisher","award":["NRF-2017R1A2B4009387"],"award-info":[{"award-number":["NRF-2017R1A2B4009387"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Renal ischemia reperfusion (IR) injury is a major cause of acute kidney injury (AKI) that is often complicated by multiple organ failure of the liver and intestine. The mineralocorticoid receptor (MR) is activated in patients with renal failure associated with glomerular and tubular damage. We thus investigated whether canrenoic acid (CA), a mineralocorticoid receptor (MR) antagonist, protects against AKI-induced hepatic and intestinal injury, suggesting the underlying mechanisms. Mice were divided into five groups: sham mice, mice subjected to renal IR, and mice pretreated with canrenoic acid (CA; 1 or 10 mg\/kg) 30 min prior to renal IR. At 24 h after renal IR, the levels of plasma creatinine, alanine aminotransferase and aldosterone were measured, and structural changes and inflammatory responses of the kidney, liver, and intestine were analyzed. We found that CA treatment reduced plasma creatinine levels, tubular cell death and oxidative stress induced by renal IR. CA treatment also decreased renal neutrophil infiltration and inflammatory cytokine expression and inhibited the release of high-mobility group box 1 induced by renal IR. Consistently, CA treatment reduced renal IR-induced plasma alanine transaminase, hepatocellular injury and neutrophil infiltration, and inflammatory cytokine expression. CA treatment also decreased small intestinal cell death, neutrophil infiltration and inflammatory cytokine expression induced by renal IR. Taken together, we conclude that MR antagonism by CA treatment protects against multiple organ failure in the liver and intestine after renal IR.<\/jats:p>","DOI":"10.3390\/ijms24043413","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T01:59:43Z","timestamp":1675907983000},"page":"3413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mineralocorticoid Receptor Antagonism Attenuates Multiple Organ Failure after Renal Ischemia and Reperfusion in Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Eun Jung","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jihyun","family":"Je","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8337-4969","authenticated-orcid":false,"given":"Theodomir","family":"Dusabimana","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung Pil","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Sciences, Gyeongsang National University Graduate School, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Sciences, Gyeongsang National University Graduate School, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7181-3696","authenticated-orcid":false,"given":"Hwajin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6149-5284","authenticated-orcid":false,"given":"Sang Won","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Sciences, Gyeongsang National University Graduate School, Jinju 52727, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrneph.2017.2","article-title":"Acute kidney disease and renal recovery: Consensus report of the Acute Disease Quality Initiative (ADQI) 16 Workgroup","volume":"13","author":"Chawla","year":"2017","journal-title":"Nat. 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