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Amifostine is the only FDA-approved chemoprotective drug; however, its clinical application is limited because of side effects. The small-molecule antioxidant XH-003, an acute radiation syndrome- (ARS-) protective drug independently developed in our laboratory, with 100% intellectual property rights, overcomes the side effects of amifostine but retains its high efficacy. In this study, XH-003 showed a chemoprotective effect similar to that of amifostine. A mechanistic study showed that XH-003 could significantly reduce cisplatin-induced increases in serum creatinine and urea nitrogen, increase the activity of antioxidant enzymes (SOD, CAT, and GSH-Px), reduce oxidative stress and tissue inflammation, and alleviate renal tissue damage by blocking the activity of the mitochondrial apoptosis pathway. Most importantly, XH-003 could reduce the accumulation of cisplatin in renal tissue by regulating the expression of proteins involved in cisplatin uptake and excretion, such as organic cation transporter 2 and MRP2. Moreover, in an <jats:italic>in vivo<\/jats:italic> xenotransplantation model, XH-003 did not interfere with the antitumor effect of cisplatin. These data provide strong evidence that the ARS-protective agent has a great potential for protecting against chemotherapy-induced toxicity. Thus, XH-003 can be considered in antitumor therapy.<\/jats:p>","DOI":"10.1155\/2020\/9820168","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T23:32:35Z","timestamp":1587425555000},"page":"1-12","source":"Crossref","is-referenced-by-count":10,"title":["Renoprotective Effects of a New Free Radical Scavenger, XH-003, against Cisplatin-Induced Nephrotoxicity"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4889-2234","authenticated-orcid":true,"given":"Ya-Hong","family":"Liu","sequence":"first","affiliation":[{"name":"Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 238, Baidi Road, Tianjin, 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