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Calcium channel blockers (CCBs) have been reported to exert a renal protective effect. This study aims to investigate the role of cilnidipine, a novel CCBs, on CIN by regulating the calcium\/calmodulin\u2010dependent protein kinase \u2161(CaMK\u2161)\/mitochondrial permeability transition pore\u00a0(mPTP) pathway. Here, iohexol, a representative contrast media, was used to establish CIN model. KN\u201093 (CaMK\u2161 inhibitor) and atractyloside (mPTP opener) were administered in rats, and CaMK\u2161 overexpression was used in Human proximal tubular epithelial cells. Markers of renal injury (serum creatinine, blood urea nitrogen, and urinary NAGL), hematoxylin\u2010eosin stain, oxidative stress (ROS, superoxide dismutase\u00a0[SOD], and malondialdehyde [MDA] levels), cell death (MTT and terminal deoxynucleotidyl transferase\u2010mediated deoxyuridine triphosphate nick end labeling\u00a0[TUNEL]), mitochondrial function (mPTP, mitochondrial membrane potential\u00a0[MMP], and ATP) were assessed. Western blots were used to measure the expression levels of Bax\/Bcl\u20102, caspase\u20103, CaMK\u2161\/mPTP signaling pathways. Results showed that cilnidipine markedly improved kidney function, and alleviated tubular cell apoptosis, oxidative stress and mitochondrial damage induced by iohexol in vitro and in vivo. The underlying mechanism may be that cilnidipine relieved CaMK\u2161 activation and mPTP opening induced by iohexol. All of these protective effects of cilnidipine were attenuated by CaMK\u2161 overexpression and atractyloside (mPTP opener) pretreatment. Moreover, KN\u201093 (CaMK\u2161 inhibitor) treatment showed a similar renal protective effect with cilnidipine, while the protective effect of cilnidipine on kidney in CIN rats was not further suppressed by KN\u201093 cotreatment. These in vitro and in vivo results point toward\u00a0the fact that cilnidipine might be a novel therapeutic drug against contrast\u2010induced nephrotoxicity in a CaMK\u2161\u2010dependent manner.<\/jats:p>","DOI":"10.1002\/jbt.23238","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T00:24:28Z","timestamp":1665188668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["An in vivo and in vitro model on the protective effect of cilnidipine on contrast\u2010induced nephropathy via regulation of apoptosis and CaMK\u2161\/mPTP pathway"],"prefix":"10.1002","volume":"37","author":[{"given":"Kun","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Can","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xurui","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0294-6268","authenticated-orcid":false,"given":"Xiaocong","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"},{"name":"Center of Clinical Pharmacology, The Third Xiangya Hospital Central South University Changsha City Hunan Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,10,7]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2021.03.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2002.32766"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.06.009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.04.022"},{"key":"e_1_2_9_6_1","first-page":"2","volume":"6","author":"Yin W. 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