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

Abstract EN

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.