Circadian Cyp3a11 metabolism contributes to chronotoxicity of hypaconitine in mice

Hypaconitine administration in mice showed time-dependent toxicity, being more severe during the light phase.

• Toxicity levels of hypaconitine varied based on the time of day, with increased severity observed during the light phase compared to the dark phase.
• The observed chronotoxicity was linked to differences in how the body processes hypaconitine at different times of day.
• Diurnal expression of the enzyme Cyp3a11, crucial for detoxifying hypaconitine in the liver, influenced its metabolism.
• Bmal1 disruption in mice eliminated the daily rhythm of Cyp3a11 expression and the associated time-dependent toxicity of hypaconitine.
• Circadian variations in Cyp3a11 activity play a role in the chronotoxic effects of hypaconitine.

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