Possible involvement of oxidative stress in 5-fluorouracil-mediated myelosuppression in mice

Satoshi Numazawa, Kazuko Sugihara, Shota Miyake, Hirono Tomiyama, Ayako Hida, Misato Hatsuno, Masayuki Yamamoto, Takemi Yoshida

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Certain chemotherapeutic agents subject cells to oxidative stress, thereby promoting adverse effects. However, the molecular machinery governing 5-fluorouracil (5-FU)-mediated myelotoxicity is obscure. The purpose of this study was to clarify whether 5-FU-induced myelotoxicity is a cause of oxidative stress. Treatment of mice with 5-FU (75 mg/kg, i.p.) caused a significant induction of haem oxygenase-1 and a decrease in glutathione contents in bone marrow cells, both of which are the indicators of oxidative stress. The 5-FU-mediated decrease in the myeloid colony formation was intensified in Nrf2-/- mice, in which antioxidant proteins were down-regulated. N-Acetylcysteine reversed the 5-FU-induced decreases in the glutathione content, number of bone marrow cells per femur and myeloid colony formation. Results from the present study reveal that 5-FU induces oxidative stress in bone marrow, which is involved, at least in part, in myelotoxicity in mice. Therefore, Nrf2-dependent genes as well as glutathione levels in bone marrow could be therapeutic targets for decreasing such side-effects in 5-FU-based chemotherapy.

Original languageEnglish
Pages (from-to)40-45
Number of pages6
JournalBasic and Clinical Pharmacology and Toxicology
Volume108
Issue number1
DOIs
Publication statusPublished - 2011 Jan

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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