{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T23:32:10Z","timestamp":1787959930543,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":211,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017959","name":"Health Commission of Hebei Province","doi-asserted-by":"publisher","award":["20180398"],"award-info":[{"award-number":["20180398"]}],"id":[{"id":"10.13039\/100017959","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    Vancomycin is the first\u2010line treatment for\n                    <jats:italic>MRSA<\/jats:italic>\n                    infection, and high plasma concentration can cause nephrotoxicity. The aim of the study was to determine the correlation between intracellular vancomycin concentration and HK\u20102 cytotoxicity and explore omeprazole\u2019s protective effect.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    The activity of HK\u20102 cells was detected, HPLC method was established and verified, and the vancomycin concentrations in the intracellular and extracellular fluids of HK\u20102 cells were determined. Western blot was used to investigate the expressions of P\u2010glycoprotein (P\u2010gp) and organic cation transporter\u20102 (OCT\u20102) transporters. Blood urea nitrogen (BUN), blood creatinine (CRE),\n                    <jats:italic>N<\/jats:italic>\n                    \u2010acetyl\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010\n                    <jats:sc>d<\/jats:sc>\n                    \u2010glucosaminidase (NAG), and kidney injury molecule\u20101 (KIM\u20101) of rats in the vancomycin group and drug combination group were determined; the kidney tissue pathological examination and renal injury score were performed.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    The HPLC method met the requirements for biological sample determination. The cytotoxicity of vancomycin in HK\u20102 cells was concentration\u2010dependent within 1\u201320\u2009mg\/mL; omeprazole could reduce the intracellular accumulation of vancomycin. Western blot assay confirmed that omeprazole increased intracellular vancomycin efflux by upregulating P\u2010gp expression and inhibited its intracellular transport by downregulating OCT\u20102 expression. Vancomycin increased renal function indicators and pathological injury score in rats, while there was a significant decrease in the drug combination group, together with alleviated renal tissue damage.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    Intracellular accumulation of vancomycin can cause damage to HK\u20102 cells and induce vancomycin\u2010related nephrotoxicity in rats. Omeprazole can reduce vancomycin cytotoxicity by upregulating P\u2010gp expression and inhibiting OCT\u20102 expression.\n                  <\/jats:p>","DOI":"10.1155\/bmri\/3520935","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T12:34:50Z","timestamp":1753965290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Protective Effect of Omeprazole on Vancomycin Cytotoxicity in HK\u20102 Cells and Renal Injury in 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