{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T11:18:45Z","timestamp":1761304725533,"version":"build-2065373602"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004172","name":"Mersin University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004172","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cisplatin is widely used in pediatric oncology but is limited by its dose-dependent nephrotoxicity. The renin\u2013angiotensin\u2013aldosterone system (RAAS) has been implicated in cisplatin-induced renal injury. Losartan, an angiotensin II receptor blocker, may offer renal protection; however, its effects on apoptosis and regeneration in this context remain unclear. This study aimed to investigate the potential protective role of losartan against cisplatin-induced nephrotoxicity, specifically by assessing its impact on apoptosis and tubular regeneration. Fifteen female BALB\/c mice were randomly assigned to three groups (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20095 per group): Control, cisplatin (12.7\u00a0mg\/kg, i.p., single dose), and cisplatin\u2009+\u2009losartan (10\u00a0mg\/kg\/day, oral). Losartan was administered for nine consecutive days, starting 4\u00a0days before cisplatin exposure. Histopathological examination, active caspase-3 immunostaining (for apoptosis), and 5-bromo-2-deoxyuridine (BrdU) labeling (for cell proliferation) were performed. Glomerular and tubular injury scores, caspase-3 H-scores, and BrdU-positive cell counts were statistically analyzed using the Kruskal\u2013Wallis H and Mann\u2013Whitney\n                    <jats:italic>U<\/jats:italic>\n                    tests. Cisplatin significantly increased glomerular (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.006) and tubular injury scores (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.007), elevated active caspase-3 expression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.002), and reduced BrdU-positive cell counts (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009) compared to control. Losartan co-treatment significantly reduced glomerular (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.005,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008) and tubular injury (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.008, v) and decreased caspase-3 expression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009). Additionally, BrdU-positive cell counts were significantly higher in the cisplatin\u2009+\u2009losartan group compared to both control and cisplatin groups (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009), indicating enhanced regeneration. Losartan mitigates cisplatin-induced nephrotoxicity by suppressing apoptosis and promoting tubular regeneration. These findings support the potential therapeutic role of RAAS inhibition in preventing cisplatin-associated renal injury.\n                  <\/jats:p>","DOI":"10.1007\/s00210-025-04150-7","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T03:21:14Z","timestamp":1746242474000},"page":"15351-15362","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Assessment of protective effect of the losartan against cisplatin-induced nephrotoxicity in mice"],"prefix":"10.1007","volume":"398","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1885-6611","authenticated-orcid":false,"given":"Sel\u00e7uk","family":"Teke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-7203","authenticated-orcid":false,"given":"G\u00fclsen","family":"Bayrak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-4575","authenticated-orcid":false,"given":"Erdem","family":"Ak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-9326","authenticated-orcid":false,"given":"Ali Can","family":"Korkmaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1759-3052","authenticated-orcid":false,"given":"\u015eakir Necat","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-9276","authenticated-orcid":false,"given":"Ali","family":"Deliba\u015f","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,5,3]]},"reference":[{"issue":"9","key":"4150_CR1","doi-asserted-by":"publisher","first-page":"1927","DOI":"10.3390\/molecules29091927","volume":"29","author":"SA Abass","year":"2024","unstructured":"Abass SA, Elgazar AA, El-kholy SS, El-Refaiy AI, Nawaya RA, Bhat MA, Farrag FA, Hamdi A, Balaha M, El-Magd MA (2024) Unraveling the nephroprotective potential of papaverine against cisplatin toxicity through mitigating oxidative stress and \u0131nflammation: \u0131nsights from \u0131n silico, \u0131n vitro, and \u0131n vivo \u0131nvestigations. 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Approval was granted by the Mersin University Animal Experiment Local Ethics Committee (Mersin University Ethics Committee, protocol number: 52602694\u2013050\/E22273; 2016\/02).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}