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

Abstract

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.