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Updated: Jun 10, 2026
Screening Assay for Oxidative Stress in a Feline Astrocyte Cell Line, G355-5
Published on: July 13, 2011
Possible involvement of oxidative stress in 5-fluorouracil-mediated myelosuppression in mice
Satoshi Numazawa1, Kazuko Sugihara, Shota Miyake
1Department of Biochemical Toxicology, Showa University School of Pharmacy, Shinagawa, Tokyo, Japan. numazawa@pharm.showa-u.ac.jp
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.
Insights
5-fluorouracil (5-FU) chemotherapy causes oxidative stress in bone marrow, leading to myelotoxicity. Boosting glutathione and Nrf2-dependent genes may mitigate these chemotherapy side effects.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Chemotherapeutic agents can induce cellular oxidative stress, contributing to adverse effects.
- The precise mechanisms behind 5-fluorouracil (5-FU)-induced myelotoxicity remain unclear.
- Oxidative stress is implicated in various drug-induced toxicities.
Purpose of the Study:
- To investigate whether 5-FU-induced myelotoxicity is a consequence of oxidative stress.
- To elucidate the role of oxidative stress in 5-FU's impact on bone marrow.
Main Methods:
- Mice were treated with 5-FU (75 mg/kg, i.p.).
- Assessed indicators of oxidative stress: haem oxygenase-1 induction and glutathione content in bone marrow cells.
- Examined myeloid colony formation in wild-type and Nrf2(-/-) mice.
- Evaluated the effect of N-Acetylcysteine (NAC) administration.
Main Results:
- 5-FU treatment significantly increased haem oxygenase-1 and decreased glutathione levels in bone marrow cells.
- Myelotoxicity, indicated by reduced myeloid colony formation, was more severe in Nrf2(-/-) mice.
- N-Acetylcysteine treatment ameliorated 5-FU-induced decreases in glutathione, bone marrow cellularity, and myeloid colony formation.
Conclusions:
- 5-FU induces oxidative stress in mouse bone marrow, contributing to myelotoxicity.
- Nrf2-dependent genes and glutathione levels represent potential therapeutic targets for mitigating 5-FU side effects.
- Targeting oxidative stress pathways could offer a strategy to improve 5-FU chemotherapy tolerability.
