Supplementary file 1_Effects of music elements on mycophenolate glucuronidation in rat liver microsomes.pdf

Enzyme kinetics in FT IR AH versus controls were determined across MPA concentrations (0–320 μg/mL). mRNA and protein expression of the AcMPAG-forming enzyme (UDP-glucuronosyltransferase UGT2B1) and other expressed UGTs were analysed.</p>Results<p>MPAG formation was unaffected by any music combination, whereas niflumic acid (100 μM, positive control) reduced it by ∼67%. AcMPAG formation was significantly reduced by FT IR (42.5 ± 14.4%; mean ± SEM; p < 0.05) and further reduced with added AH (74.4 ± 10.8%; p < 0.005).

For MPAG, V_max and CL_int were comparable to controls, with a modestly higher K_m. For AcMPAG, V_max and CL_int decreased by 89.7 ± 46.4% and 91.5 ± 29.7%, respectively (p < 0.05, n = 7 [3 males, 4 females]), with no change in K_m. No sex differences in kinetic parameters were observed for either analyte.

Inter-composer differences in MPA glucuronidation could be explained by the legato (continuous)-to-staccato (intermittent) articulation ratio. Hepatic Ugt2b1 mRNA and protein expression were unchanged after FT IR AH exposure, as were hepatic Ugt1a1, Ugt1a5, Ugt1a6, Ugt1a7, and Ugt2b12 mRNA.</p>Conclusion<p>Our novel findings indicate that specific music elements (FT IR AH) reduced generation of the minor, toxic AcMPAG without affecting formation of the major, inactive MPAG.

This is potentially therapeutically beneficial, as the adverse effects of MPA might be selectively attenuated without altering its clearance or therapeutic outcomes.</p>