Effects of NO donors on CYP2C22 expression and retinoid metabolism in hepatocytes. (A) Western blot showing time course of downregulation of CYP2C22 protein by the NO donor NOC18 in cultured hepatocytes. (B) Time courses of downregulation of CYP2C22 mRNA and protein by NOC18. Cells were treated with 500 μM NOC18 or vehicle and harvested at the indicated times. CYP2C22 data are from the blots shown in (A). *Significantly different from timed control, P < 0.05 (n = 3), t test. (C) Western blot showing concentration dependence of the NOC18 effect. Cells were treated for 12 hours with the indicated concentration. (D) Quantitative analysis of the data in (C). *Significantly different from zero time control, P < 0.05, Dunnett’s test (n = 3). (E) Effect of NO donors and IL-1 on retinoic acid–metabolizing activities of rat hepatocytes. Hepatocytes were treated with medium (control), 5 ng/ml IL-1 for 12 hours, 500 μM NOC18 for 12 hours, or 500 μM DPTA for 6 hours. The cells were harvested, and the formation of 4-OH-RA from atRA was measured in S9 fractions of the cells. The activities are shown relative to control cells. *Significantly different from control, P < 0.05, Dunnett’s test (n = 4). (F) Western blot showing CYP2C22 expression in the samples from (E).