{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T03:03:27Z","timestamp":1789614207030,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"University of Houston GEAR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Aminoglycosides and polymyxins are antibiotics with in vitro activity against MDR Gram-negative bacteria. However, their clinical use is hindered by dose-limiting nephrotoxicity. The objective of this project was to determine if zileuton can reduce nephrotoxicity associated with amikacin and polymyxin B in a rat model of acute kidney injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Sprague Dawley rats (n\u200a=\u200a10, both genders) were administered either amikacin (300 mg\/kg) or polymyxin B (20 mg\/kg) daily for 10 days. Zileuton (4 and 10 mg\/kg) was delivered intraperitoneally 15 min before antibiotic administration. Blood samples were collected at baseline and daily to determine serum creatinine concentration. Nephrotoxicity was defined as a \u22652\u00d7 elevation of baseline serum creatinine. Time-to-event analysis and log rank test were used to compare the onset of nephrotoxicity in different cohorts. Histopathological analysis was also conducted to characterize the extent of kidney injury.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Animals receiving amikacin or polymyxin B alone had nephrotoxicity rates of 90% and 100%, respectively. The overall rate was reduced to 30% in animals receiving adjuvant zileuton. The onset of nephrotoxicity associated with amikacin and polymyxin B was also significantly delayed by zileuton at 4 and 10 mg\/kg, respectively. Histopathology confirmed reduced kidney injury in animals receiving amikacin concomitant with zileuton.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our pilot data suggest that zileuton has the potential to attenuate nephrotoxicity associated with last-line antibiotics. This would allow these antibiotics to treat MDR Gram-negative bacterial infections optimally without dose-limiting constraints. Further studies are warranted to optimize drug delivery and dosing in humans.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkad246","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T04:49:07Z","timestamp":1691729347000},"page":"2435-2441","source":"Crossref","is-referenced-by-count":6,"title":["Zileuton ameliorates aminoglycoside and polymyxin-associated acute kidney injury in an animal model"],"prefix":"10.1093","volume":"78","author":[{"given":"Cole S","family":"Hudson","sequence":"first","affiliation":[{"name":"Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy , 4849 Martin Luther King Boulevard, Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice & Translational Research, University of Houston College of Pharmacy , 4849 Martin Luther King Boulevard, Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna M","family":"Eales","sequence":"additional","affiliation":[{"name":"Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy , 4849 Martin Luther King Boulevard, Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shama","family":"Kajiji","sequence":"additional","affiliation":[{"name":"Emergent System Analytics, LLC , 24 W Main St Suite 216, Clinton, CT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacological & Pharmaceutical Sciences, University of Houston College of Pharmacy , 4849 Martin Luther King Boulevard, Houston, TX , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luan D","family":"Truong","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic 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