Circadian variation in hematotoxicity of the antineoplastic agent “5 Fluorouracil (5 FU)” in female rats and its relevance to chronotherapy

ABSTRACT

5-Fluorouracil (5-FU) is an antineoplastic drug. Although 5-FU is effective in targeting cancer cells, it also affects healthy cells, which can lead to clear haematological toxicity. The present study aimed to determine whether the haematological toxicity of 5-FU varies over a 24-hour period. Female rats were synchronised to a 12/12 light-dark (L/D) cycle. Rats were injected with 300 mg/kg 5-FU at six different circadian stages (1, 5, 9, 13, 17, 21 Zeitgebers (ZT)). The maximum rhythmic alteration was observed when 5-FU was administered at 5-ZT, while the minimum was observed at 21-ZT. These results suggest that the haematological toxicity of 5-FU is maximal when administered in the middle of the light-rest phase, while the haematological tolerance is optimal when 5-FU is administered at the end of the dark phase in rats, which corresponds to the end of the daytime activity phase in human patients. 

KEYWORDS:

• 5-Fluorouracil
• chronotoxicity
• murine
• circadian rhythm
• hematological toxicity

Acknowledgments

The authors would like to thank Ms Samia MRAD senior technician in Clinical Pharmacology Laboratory for technical assistance. This work was supported by ‘‘Le ministère de l’Enseignement Supérieur et de la Recherche Scientifique’’.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.