Western Diet Decreases Hepatic Drug Metabolism in Male LDLr^−/−ApoB^100/100 Mice

Table 2

Linear correlation coefficients between oxidation rates of two CYP substrates or between rates of two conjugation substrates and their respective values in liver samples of male LDLr^−/−ApoB^100/100 mice fed with the chow or Western diet. The rates of CYP oxidation, glucuronidation, sulfonation, or COMT with the indicated substrates were determined as described in Materials and Methods. Correlations were calculated from the data in Figures 2 and 3.

Oxidation substrate 1-oxidationsubstrate 2	Correlation coefficient r^2	value
7-ethoxyresorufin (C1)-3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)	0.1597	0.1003
7-ethoxyresorufin (C1)-3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)	0.1265	0.1475
7-ethoxyresorufin (C1)-3-(3-methoxyphenyl)coumarin (C6)	0.3555	0.0090
7-ethoxyresorufin (C1)-3-(3-benzyloxo)phenyl-7-methoxycoumarin (C7)	0.07485	0.2720
7-ethoxyresorufin (C1)-coumarin (C4)	0.1783	0.0809
7-ethoxyresorufin (C1)-7-pentoxyresorufin (C5)	0.07366	0.2760
3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)-3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)	0.7141	<0.0001
3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)-3-(3-methoxyphenyl)coumarin (C6)	0.02517	0.5295
3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)-3-(3-benzyloxo)phenyl-7-methoxycoumarin(C7)	0.8740	<0.0001
3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)-coumarin (C4)	0.7474	<0.0001
3-(3-fluoro-4-hydroxyphenyl)-6-methoxycoumarin (C3)-7-pentoxyresorufin (C5)	0.2930	0.0203
3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)-3-(3-methoxyphenyl)coumarin (C6)	0.04947	0.3750
3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)-3-(3-benzyloxo)phenyl-7-methoxycoumarin(C7)	0.6072	0.0001
3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)-coumarin (C4)	0.4735	0.0016
3-(4-trifluoromethoxyphenyl)-6-methoxycoumarin (C2)-7-pentoxyresorufin (C5)	0.5685	0.0003
3-(3-methoxyphenyl)coumarin (C6)-3-(3-benzyloxo)phenyl-7-methoxycoumarin (C7)	0.004639	0.7883
3-(3-methoxyphenyl)coumarin (C6)-coumarin (C4)	0.1546	0.1065
3-(3-methoxyphenyl)coumarin (C6)-7-pentoxyresorufin (C5)	0.2151	0.0526
Coumarin (C4)-3-(3-benzyloxo)phenyl-7-methoxycoumarin (C7)	0.7541	<0.0001
Coumarin (C4)-7-pentoxyresorufin (C5)	0.2597	0.0308
3-(3-benzyloxo)phenyl-7-methoxycoumarin (C7)-7-pentoxyresorufin (C5)	0.1527	0.1089
Conjugation substrate 1-conjugation substrate 2
Glucuronidation 7-hydroxy-4-trifluoromethylcoumarin (G1)-3-(1H-1, 2, 4-triazol-1-yl)-7-hydroxycoumarin (G2)	0.03156	0.4807
Sulfonation 7-hydroxy-4-trifluoromethylcoumarin (S1)-3-(4-methylphenyl)-7-hydroxycoumarin (S2)	0.0006785	0.9183
COMT cytosol (Cc)-COMT microsomes (Cm)	0.06438	0.3096

Values in bold indicate a statistically significant correlation. Letter number abbreviations, e.g., C1 in the brackets after the substrate point to the reactions of Figure 4. Values in bold indicate a statistically significant correlation. Letter number abbreviations, e.g., C1 in the brackets after the substrate point to the reactions in Figure 4.