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Metabolic Brain Disease

, Volume 23, Issue 3, pp 325–333 | Cite as

Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats

  • Gregory W. KonatEmail author
  • Michal Kraszpulski
  • Isaac James
  • Han-Ting Zhang
  • Jame Abraham
Original Paper

Abstract

Although cognitive dysfunction manifested by severe memory and attention deficits has been reported in up to 70% of cancer patients undergoing chemotherapy, the mechanisms of this serious side effect have not been defined. In particular, it has not been decisively resolved whether the dysfunction is attributable to the chemotherapy or to the malignancy itself. In the present study we tested whether cognitive dysfunction can be induced in an experimental setting by the administration of commonly used chemotherapeutics to rats. Female 10 month old Sprague–Dawley rats were injected intraperitoneally with a combination of 2.5 mg/kg of adriamycin (ADR) and 25 mg/kg of cytoxan (CTX). A total of four doses were given at weekly intervals. The control group was treated with saline only. No mortality and no apparent morbidity were observed in either group. However, the chemotherapeutic treatment severely impaired memory function of rats as measured by a passive avoidance test. This memory deficiency was fully prevented by the administration of an antioxidant, N-acetyl cysteine (NAC) injected subcutaneously three times a week at 200 mg/kg in the course of chemotherapeutic treatment. These results indicate that chemotherapeutic agents alone, i.e., in the absence of malignancy, damage the brain resulting in memory dysfunction. Moreover, the results strongly indicate that the damaging effect is mediated by oxidative stress, as memory dysfunction is preventable by the co-administration of NAC.

Keywords

Adriamycin Cytoxan N-Acetyl cysteine Memory impairment 

Notes

Acknowledgements

This study was supported by DOD research grant DAMD17-02-1-0621.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Gregory W. Konat
    • 1
    Email author
  • Michal Kraszpulski
    • 1
  • Isaac James
    • 1
  • Han-Ting Zhang
    • 2
  • Jame Abraham
    • 3
  1. 1.Department of Neurobiology and AnatomyWest Virginia University School of MedicineMorgantownUSA
  2. 2.Department of Behavioral Medicine and PsychiatryWest Virginia University School of MedicineMorgantownUSA
  3. 3.Mary Babb Randolph Cancer CenterWest Virginia University School of MedicineMorgantownUSA

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