{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T13:26:15Z","timestamp":1793453175429,"version":"4.5.0"},"reference-count":60,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Colistin (Cst) is one of the antimicrobial peptides and is reserved for use against multi\u2010drug\u2010resistant Gram\u2010negative bacteria. However, the clinical value of Cst is limited by its nephrotoxic adverse effects. Caffeic acid phenethyl ester (CAPE) is a honeybee propolis flavonoid recognised for its diverse pharmacological potential. It has demonstrated d antioxidant and anti\u2010inflammatory properties, as well as protective effects against chemically induced toxicity in variuos biological systems. This study aimed to investigate the impact of CAPE on nephrotoxicity induced in rats by Cst.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Animals were randomly divided into five groups. Group 1 served as control, group 2 received CAPE (10\u2009mg\/kg) orally, group 3 received Cst IP, group 4 received Cst\u2009+\u2009CAPE (5\u2009mg\/kg) and group 5 received Cst\u2009+\u2009CAPE (10\u2009mg\/kg). All treatments were given daily for 10 consecutive days.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CAPE notably attenuated Cst\u2010inducednephrotoxicity as shown by reducing urea serum levels, creatinine, cystatin C, urinary protein contents and urinary N\u2010acetyl\u2010\u03b2\u2010D\u2010glucosaminidase (NAG). This was confirmed by histological investigations that indicated amelioration of histopathological changes in the kidney architecture as well as the deposition of collagen in renal tissues. CAPE exhibited antioxidant effects supported by the prevention of rise in Cst\u2010induced lipid peroxidation and depletion of superoxide dismutase and catalase enzymatic activities. In addition, CAPE inhibited the expression of the inflammatory markers including tumour necrosis factor\u2010\u03b1, nuclear factor kappa B and interleukin\u20106. These actions were associated with modulation of messenger ribonucleic acid (mRNA) expression of\n                      <jats:italic>Bax<\/jats:italic>\n                      and\n                      <jats:italic>Bcl\u20102<\/jats:italic>\n                      in favour of anti\u2010apoptosis. CAPE inhibited Cst\u2010induced rise in forkhead box O1 (FOXO1) expression and downregulation of nuclear factor erythroid 2\u2013related factor 2 (Nrf2) and Sirtuin 1 (Sirt1) immune\u2010expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CAPE protects against nephrotoxicity induced by Cst in ratsprimarily through its antioxidant, antiinflammatory and antiapoptotic activities. These pritective effects are mediated\u00a0via modulation of FOXO1\/Nrf2\/Sirt1 axis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1440-1681.70000","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T21:00:05Z","timestamp":1729803605000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Caffeic acid phenethyl ester ameliorates colistin\u2010induced nephrotoxicity in rats via modulation of\n                    <scp>FOXO1<\/scp>\n                    \/Nrf2\/Sirt1 axis"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-0742","authenticated-orcid":false,"given":"Mohammed Z.","family":"Nasrullah","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy King Abdulaziz University  Jeddah Saudi 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