Tempol reduces the therapeutic effect of cyclophosphamide on an experimental tumour model

Free Radic Res. 2009 Jul;43(7):685-90. doi: 10.1080/10715760902998198.

Abstract

The nitroxyl radical 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol) is reported to elicite some effects on different biological models. This paper studied the influence of Tempol on the therapeutic action of an alkylating agent cyclophosphamide (CP) in the transplantable murine lymphosarcoma LS. When administered exactly before CP, Tempol exerted no influence on efficacy of the tumour therapy but significantly reduced it under a single or multiple preliminary injections 1-3 days before CP. This regimen of Tempol administration is found to elevate the activity of aldehyde dehydrogenase in the liver, the enzyme which is known to reduce the yield of the activated metabolite(s) of CP.

MeSH terms

  • Aldehyde Dehydrogenase / metabolism
  • Animals
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Antioxidants / pharmacology*
  • Cyclic N-Oxides / pharmacology*
  • Cyclophosphamide / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / enzymology
  • Lymphoma, Non-Hodgkin / pathology
  • Male
  • Mice
  • Mice, Inbred CBA
  • Sarcoma, Experimental / drug therapy*
  • Sarcoma, Experimental / enzymology
  • Sarcoma, Experimental / pathology
  • Spin Labels
  • Survival Rate

Substances

  • Antineoplastic Agents, Alkylating
  • Antioxidants
  • Cyclic N-Oxides
  • Spin Labels
  • Cyclophosphamide
  • Aldehyde Dehydrogenase
  • tempol