Circadian rhythm and seasonal dependence in the toxicological response of mice to epirubicin.

Abstract:

:Compared to doxorubicin, equimolar epirubicin toxicity is reduced by about 50% by the epimerization of a hydrogen and hydroxyl group at the 4' position of the anthracycline sugar moiety. The circadian timing of doxorubicin administration markedly affects its lethal and sub-lethal bone marrow and gut toxicities in mice, as well as the severity of its clinical toxicity. We tested whether the timing of administration of equitoxic epirubicin doses similarly affected the toxicological response in female CD2F1 mice. A large and highly reproducible effect of the circadian stage of administration was documented with best drug tolerance occurring during the first half of the daily rest (light) span of the animals. In addition to this circadian rhythm, a significant seasonal effect was found with significantly fewer deaths occurring after epirubicin was given in the Summer, as compared to the Winter. Safest circadian timing for epirubicin is statistically significantly earlier in the day than for doxorubicin, while their seasonal patterns are quite similar.

journal_name

Invest New Drugs

authors

Mormont MC,von Roemeling R,Sothern RB,Berestka JS,Langevin TR,Wick M,Hrushesky WJ

doi

10.1007/BF00173645

subject

Has Abstract

pub_date

1988-12-01 00:00:00

pages

273-83

issue

4

eissn

0167-6997

issn

1573-0646

journal_volume

6

pub_type

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