Suramin protects from cisplatin-induced acute kidney injury

Tess V. Dupre, Mark A. Doll, Parag P. Shah, Cierra N. Sharp, Alex Kiefer, Michael T. Scherzer, Kumar Saurabh, Doug Saforo, Deanna Siow, Lavona Casson, Gavin E. Arteel, Alfred Bennett Jenson, Judit Megyesi, Rick G. Schnellmann, Levi J. Beverly, Leah J. Siskind

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Cisplatin, a commonly used cancer chemotherapeutic, has a dose-limiting side effect of nephrotoxicity. Approximately 30% of patients administered cisplatin suffer from kidney injury, and there are limited treatment options for the treatment of cisplatin-induced kidney injury. Suramin, which is Federal Drug Administration-approved for the treatment of trypanosomiasis, improves kidney function after various forms of kidney injury in rodent models. We hypothesized that suramin would attenuate cisplatin-induced kidney injury. Suramin treatment before cisplatin administration reduced cisplatin-induced decreases in kidney function and injury. Furthermore, suramin attenuated cisplatininduced expression of inflammatory cytokines and chemokines, endoplasmic reticulum stress, and apoptosis in the kidney cortex. Treatment of mice with suramin 24 h after cisplatin also improved kidney function, suggesting that the mechanism of protection is not by inhibition of tubular cisplatin uptake or its metabolism to nephrotoxic species. If suramin is to be used in the context of cancer, then it cannot prevent cisplatin-induced cytotoxicity of cancer cells. Suramin did not alter the dose-response curve of cisplatin in lung adenocarcinoma cells in vitro. In addition, suramin pretreatment of mice harboring lung adenocarcinomas did not alter the initial cytotoxic effects of cisplatin (DNA damage and apoptosis) on tumor cells. These results provide evidence that suramin has potential as a renoprotective agent for the treatment/prevention of cisplatin-induced acute kidney injury and justify future long-term preclinical studies using cotreatment of suramin and cisplatin in mouse models of cancer.

Original languageEnglish (US)
Pages (from-to)F248-F258
JournalAmerican Journal of Physiology - Renal Physiology
Volume310
Issue number3
DOIs
StatePublished - Feb 1 2016
Externally publishedYes

Keywords

  • Acute kidney injury
  • Cisplatin
  • Renoprotective strategies
  • Suramin

ASJC Scopus subject areas

  • Physiology
  • Urology

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