Fig. 4.

Effect of pravastatin co-treatment on alendronate-mediated suppression of phenobarbital-inducible CYP2B expression. A. At 48 hr after plating, primary cultured rat hepatocytes were incubated for 48 hr in medium containing 100 μM phenobarbital (PB) or PB and 30 μM pravastatin (Prava), alone (0) or in combination with 10, 30, 60 or 100 μM alendronate. After treatment, hepatocytes were harvested for measurement of CYP2B mRNA levels by northern blot hybridization. Each bar represents the mean ± range (data are from two independent hepatocyte preparations) CYP2B mRNA content as a percentage of either the corresponding group treated with PB alone (PB, 0) or with PB+Prava alone (PB+Prava, 0). B and C. Primary cultured rat hepatocytes were incubated for 48 hr in medium alone (UT) or containing 100 μM PB or 0.1 μM squalestatin 1 (Squal 1), alone or in combination with one or more of the following: 30 μM Prava, 60 μM alendronate (ALN) or 10 mM mevalonate (MVA). After treatment, hepatocytes were harvested for the measurement of CYP2B mRNA and immunoreactive protein contents (B) and PROD activities (C). PROD activities represent the mean ± sd of triplicate measurements. Comparable results were obtained in a second hepatocyte preparation.