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Updated: Dec 22, 2025
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Renoprotective Effects of a New Free Radical Scavenger, XH-003, against Cisplatin-Induced Nephrotoxicity
Ya-Hong Liu1, Kui Li1, Hong-Qi Tian1
1Tianjin 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, China.
Abstract:
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.
Insights
The novel antioxidant XH-003 protects against cisplatin-induced acute kidney injury by reducing oxidative stress and inflammation. This promising chemoprotective agent, XH-003, does not impede chemotherapy
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Cisplatin chemotherapy causes significant acute kidney injury (25-30% incidence).
- Amifostine is the sole FDA-approved chemoprotective agent, but its use is limited by side effects.
- There is a critical need for effective and safe chemoprotective strategies against cisplatin nephrotoxicity.
Purpose of the Study:
- To evaluate the chemoprotective efficacy of XH-003, a novel small-molecule antioxidant.
- To elucidate the mechanisms underlying XH-003's protective effects against cisplatin-induced kidney damage.
- To assess XH-003's impact on cisplatin's antitumor activity in vivo.
Main Methods:
- Comparative study of XH-003 and amifostine in a chemoprotection model.
- Assessment of renal function markers (serum creatinine, urea nitrogen) and antioxidant enzyme activity (SOD, CAT, GSH-Px).
- Evaluation of oxidative stress, inflammation, mitochondrial apoptosis, and cisplatin accumulation in renal tissue.
- In vivo xenotransplantation model to test XH-003's effect on cisplatin's antitumor efficacy.
Main Results:
- XH-003 demonstrated chemoprotective effects comparable to amifostine.
- XH-003 significantly reduced cisplatin-induced increases in serum creatinine and urea nitrogen.
- XH-003 enhanced antioxidant enzyme activity, reduced oxidative stress, inflammation, and renal tissue damage.
- XH-003 inhibited the mitochondrial apoptosis pathway and reduced cisplatin accumulation in renal tissue.
- XH-003 did not interfere with cisplatin's antitumor effect in vivo.
Conclusions:
- XH-003 effectively protects against cisplatin-induced acute kidney injury.
- The protective mechanism involves reducing oxidative stress, inflammation, and apoptosis, and modulating cisplatin transport.
- XH-003 is a promising chemoprotective agent with potential for integration into antitumor therapy.
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