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Zoledronic acid has also gained a place in cancer treatment due to its cytotoxic and antiproliferative effects in many cancer cells. Although zoledronic acid is considered safe, kidney damage is still one of the concerns in therapeutic doses. In the study, the aim was to assess the nephrotoxic profiles of zoledronic acid in the human embryonic kidney (HEK\u2010293) cells. Cytotoxicity evaluation was performed by 3\u2010[4,5\u2010dimethylthiazol\u20102\u2010yl]\u22122,5\u2010diphenyl\u2010tetrazolium bromide\u00a0(MTT) and neutral red uptake\u00a0tests, while oxidative stress was performed by reactive oxygen species\u00a0(ROS) production via flow cytometry, and the incomprehensible evaluation of ROS\u2010related genes by RT\u2010PCR and apoptosis was performed with Annexin\u2010PI analysis in flow cytometry. The obtained result showed that zoledronic acid inhibited cell viability (IC<jats:sub>50<\/jats:sub> values were determined as 273.16\u202f by MTT) and cell proliferation in a concentration\u2010dependent manner, induced ROS\u00a0production, caused glutathione\u00a0depletion, and increased oxidative stress index and endoplasmic reticulum (ER) stress, indicating severe cellular stress. The expression levels of oxidative damage (<jats:italic>L\u2010fabp<\/jats:italic>, <jats:italic>\u03b1\u2010GST<\/jats:italic>, <jats:italic>Nrf2<\/jats:italic>, and <jats:italic>HMOX1<\/jats:italic>), ER stress (<jats:italic>CASP4, IRE1\u2010\u03b1, GADD153<\/jats:italic>, and <jats:italic>GRP78<\/jats:italic>), and apoptosis (<jats:italic>Bcl\u20102, Bax, Cyt\u2010c, p53, CASP9, CASP3, NF\u2010\u03baB, TNF\u2010\u03b1<\/jats:italic>, and <jats:italic>JNK<\/jats:italic>) related genes were altered as well as IRE1\u2010\u03b1 protein levels. Herein, we were the first to show that increased oxidative stress and ER stress resulting in apoptosis are the key molecular pathways in zoledronic acid\u2010induced nephrotoxicity equivalent to clinically administered concentrations.<\/jats:p>","DOI":"10.1002\/jbt.23083","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T10:28:04Z","timestamp":1652956084000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Zoledronic acid\u2010induced oxidative damage and endoplasmic reticulum stress\u2010mediated apoptosis in human embryonic kidney (HEK\u2010293) cells"],"prefix":"10.1002","volume":"36","author":[{"given":"Mehtap","family":"Kara","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tu\u011f\u00e7e","family":"Boran","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezgi","family":"\u00d6zta\u015f","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayse Tarbin","family":"Jannuzzi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sibel","family":"\u00d6zden","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fcl","family":"\u00d6zhan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy Istanbul University  Istanbul Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.14310\/horm.2002.1226"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067312"},{"key":"e_1_2_10_4_1","first-page":"27","volume":"3","author":"Polascik T. 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