전한울 Song, In Sik 박진경 Lee, Hyejin Han, Eunjung Park, Saemi Lee, Yunkyoung 송치만 허우영 이인균 Choi, June 2024-01-12T06:35:24Z 2024-01-12T06:35:24Z 2023-05-18 2023-07 0166-445X https://pubs.kist.re.kr/handle/201004/79892 In this study, we aimed to identify novel compounds that could afford protection against cisplatin-induced ototoxicity by employing both cell- and zebrafish (Danio rerio)-based screening platforms. We screened 923 US Food and Drug Administration-approved drugs to identify potential compounds exhibiting protective effects against cisplatin-induced ototoxicity in HEI-OC1 cells (auditory hair cell line). The screening strategy identified esomeprazole and dexlansoprazole as the primary hit compounds. Subsequently, we examined the effects of these compounds on cell viability and apoptosis. Our results revealed that esomeprazole and dexlansoprazole inhibited organic cation transporter 2 (OCT2), thus providing in vitro evidence that these compounds could ameliorate cisplatin-induced ototoxicity by directly inhibiting OCT2-mediated cisplatin transport. In vivo, the protective effects were validated using zebrafish; esomeprazole was found to decrease cisplatin-induced hair cell damage in neuromasts. Furthermore, the esomeprazole-treated group showed a significantly lower number of TUNEL-positive cells than the cisplatin-treated group. Collectively, our findings revealed that esomeprazole exerts a protective effect against cisplatin-induced hair cell damage in both HEI-OC1 cells and a zebrafish model. English Elsevier BV Protective effects of esomeprazole against cisplatin-induced ototoxicity: an in vitro and in vivo study Article 10.1016/j.aquatox.2023.106573 1 Aquatic Toxicology, v.260 Aquatic Toxicology 260 N scie scopus 001011750000001 Marine & Freshwater Biology Toxicology Marine & Freshwater Biology Toxicology Article NEPHROTOXICITY MECHANISMS INHIBITORS SCREEN SYSTEM HAIR CELL-DEATH LATERAL-LINE AUDITORY CELLS ZEBRAFISH ERDOSTEINE Cisplatin Hair cell Protective effect Esomeprazole In vitro In vivo