Effects of music on hepatic cytochrome P450 1A enzymes in Sprague Dawley rats

The cytochrome P450 (CYP) 1A subfamily, regulated by the aryl hydrocarbon receptor (AhR), is central to the bioactivation or deactivation of xenobiotics, endogenous substrates, and carcinogens. Music can alter hormonal and neurotransmitter concentrations, which are partly regulated by CYP-dependent pathways. This study investigated whether defined musical elements modulate hepatic CYP1A in male and female Sprague-Dawley rats. Animals were exposed for 24 h to music containing variations of rhythm, tempo, and harmony. Of all conditions tested, fast-tempo, irregular-rhythm, and atonal-harmony (FT-IR-AH) produced the greatest increases in hepatic CYP1A1 (7-ethoxyresorufin O-deethylase) and CYP1A2 (7-methoxyresorufin O -demethylase) activities. In the combined-sex cohort, FT-IR-AH music increased CYP1A1 maximum velocity (V max ) and intrinsic clearance (CL int ) by 3.2- and 3.1-fold, respectively, and increased CYP1A2 V max and CL int by 1.9- and 1.8-fold, respectively, without altering enzyme affinities. FT-IR-AH also increased CYP1A1 protein expression by 1.9-fold in females and 2.6-fold in males, and CYP1A2 by 1.6-fold and 1.7-fold, respectively, with concordant elevations in mRNA levels. Replication of the same music elements across different music composers yielded consistent findings, with variations in effects potentially attributed to percentages of gaps (i.e., staccato) and frequency patterns. Selective induction of AhR-regulated genes in the absence of nuclear factor erythroid 2-related factor 2-dependent antioxidant gene activation suggests that FT-IR-AH music selectively engages AhR signaling without a generalized oxidative stress response. These data identify specific music features as an external stimulus capable of modulating CYP1A expression and function, with potential implications for therapeutic responses, toxicological effects, and drug interactions. • Fast, irregular, atonal music induced hepatic CYP1A1/2 expression and activity. • Maximum velocity and intrinsic clearance increased, with enzyme affinity unchanged. • Effects likely mediated through AhR activation, without Nrf2 antioxidant response.