Cancer Chemotherapy and Pharmacology

, Volume 72, Issue 3, pp 703–707 | Cite as

The small-molecule TNF-α inhibitor, UTL-5g, delays deaths and increases survival rates for mice treated with high doses of cisplatin

  • Jiajiu Shaw
  • Joseph Media
  • Ben Chen
  • Fredrick Valeriote
Short Communication

Abstract

Purpose

UTL-5g is a novel small-molecule chemoprotector that lowers hepatotoxicity, nephrotoxicity, and myelotoxicity induced by cisplatin through TNF-α inhibition among other factors. The objective of this study was to investigate whether UTL-5g can reduce the overall acute toxicity of cisplatin and increase cisplatin tolerability in mice.

Materials and methods

BDF1 female mice were treated individually with UTL-5g (suspended in Ora-Plus) by oral gavage at 60 mg/kg, 30 min before i.p. injection of cisplatin at 10, 15, and 20 mg/kg, respectively, on Day 0. Starting from Day 1, individual mice were again treated daily by the same dose of UTL-5g for 4 consecutive days. Survivals and body weights were monitored.

Results

UTL-5g treatment increased the survival rate and delayed the time to death for mice treated with 150 % of the maximum tolerated dose (MTD) of cisplatin (15 mg/kg). Likewise, at 200 % of the MTD of cisplatin (20 mg/kg), treatment of UTL-5g increased the survival rate and delayed the time to death. Treatment of UTL-5g did not have a significant effect on weight loss induced by cisplatin, indicating that body weight may not be a sensitive-enough measure for chemoprotection of UTL-5g against cisplatin.

Conclusions

In summary, UTL-5g delayed deaths and increased survival rates of mice treated by high doses of cisplatin, indicating that UTL-5g is capable of reducing the overall acute toxicity of cisplatin and increased cisplatin tolerability in mice; this is in line with the specific chemoprotective effects of UTL-5g previously reported. Further investigation of UTL-5g in combination with cisplatin is warranted.

Keywords

UTL-5g Cisplatin Maximum tolerated dose Toxicity Animal death/survival Body weight 

Notes

Acknowledgments

This work was supported by NIH/NCI Grant 5R44CA141749-03.

Conflict of interest

None.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Jiajiu Shaw
    • 1
  • Joseph Media
    • 2
  • Ben Chen
    • 1
  • Fredrick Valeriote
    • 2
  1. 1.21st Century Therapeutic, Inc.FerndaleUSA
  2. 2.Henry Ford Health SystemDetroitUSA

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