Renoprotective Effects of a New Free Radical Scavenger, XH-003, against Cisplatin-Induced Nephrotoxicity

• Main Authors: Ya-Hong Liu, Kui Li, Hong-Qi Tian
• Format: Article
• Language: English
• Published: Hindawi Limited 2020-01-01
• Series: Oxidative Medicine and Cellular Longevity
• Online Access: http://dx.doi.org/10.1155/2020/9820168
• ISSN: 1942-0900; 1942-0994

Acute renal injury has an incidence of 25%–30% in patients with tumors who are treated with cisplatin and in patients for whom no specific drugs are available for treatment. 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 in vivo 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.