Changing the dosing schedule minimizes the disruptive effects of interferon on clock function.
Nat Med
; 7(3): 356-60, 2001 Mar.
Article
em En
| MEDLINE
| ID: mdl-11231636
ABSTRACT
The effectiveness and toxicity of many drugs vary depending on the relationship between the dosing schedule and the 24-hour rhythms of biochemical, physiological and behavioral processes. In addition, several drugs can cause alterations to the 24-hour rhythms leading to illness and altered homeostatic regulation. However, the mechanisms of this drug-based disruption of circadian 'clock' genes remain unclear. Here, we show the disruptive effect of interferon-alpha on the rhythm of locomotor activity, body temperature and clock-gene mRNA expression in the periphery and suprachiasmatic nuclei, a primary circadian pacemaker. The rhythmicity of clock genes and the photic induction of the Per gene in suprachiasmatic nuclei were disturbed by the repetitive administration of interferon-alpha. Moreover, alteration of clock function, a new concept of adverse effects, can be overcome by optimizing the dosing schedule to minimize adverse drug effects.
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Base de dados:
MEDLINE
Assunto principal:
Relógios Biológicos
/
Interferon-alfa
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article