![]() ![]() These findings should be considered when choosing an organic solvent for metabolism studies with human hepatocytes. Acetonitrile had no apparent effects on any of the on any of the activities evaluated. ![]() Methanol was found to inhibit CYP2C9 and CYP2E1 activities, but to a lesser extent than DMSO. No apparent inhibitory effects were observed for the other activities evaluated. This membrane allows the passage of the solvent, but not the solutes. At 2% DMSO, the activities for the four isoforms were approximately 40% (CYP2C9), 23% (CYP2C19), and 11% (CYP2E1) of that observed for 0.1% acetonitrile and 45% (CYP3A4) of that observed for 1% acetonitrile. We found that the formation of the porous structure could be realized by controlling the solvent polarity, which effectively increased the surface area to 222 m 2 /g and led to a good adsorption capacity for macromolecules such as lysozyme protein (>3200 mg/g). Osmosis is a process in which solvent molecules flow through a semipermeable membrane. DMSO was found to inhibit CYP2C9 and CYP2C19, CYP2E1, and CYP3A4 in a concentration-dependent manner. Previously cryopreserved human hepatocytes pooled from multiple donors were used as suspension cultures in this study. The solvents were evaluated at concentrations (v/v) of 0.1, 1, and 2%. We studied the effects of acetonitrile, dimethyl sulfoxide (DMSO), and methanol (MeOH) in human hepatocytes on cytochrome P450 (CYP) and phase II conjugation activities: phenacetin O-deethylation (CYP1A2), coumarin 7-hydroxylation (CYP2A6), tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), testosterone 6beta-hydroxylation (CYP3A4), and umbelliferone glucuronidation and sulfation. ![]()
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