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UDP-glucuronosyltransferase (UGT) enzymes catalyze the conjugation of various endogenous substances (e.g., bilirubin) and exogenous compounds (e.g., drugs). The human UGT superfamily is comprised of 2 families (UGT1 and UGT2) and 3 subfamilies (UGT1A, UGT2A, and UGT2B). Many of the individual UGT enzymes are expressed not only in liver but also in(More)
BACKGROUND Affymetrix microarrays have become increasingly popular in gene-expression studies; however, limitations of the technology have not been well established for commercially available arrays. The hybridization signal has been shown to be proportional to actual transcript concentration for specialized arrays containing hundreds of distinct probe(More)
Alpha-2 adrenergic receptors (alpha2 AR) mediate incorporation of guanosine 5'-O-(gamma-thio)triphosphate ([35S]GTPgammaS) into isolated membranes via receptor-catalyzed exchange of [35S]GTPgammaS for GDP. In the current study, we used [35S]GTPgammaS incorporation to characterize the intrinsic activity and potency of agonists and antagonists at the cloned(More)
OBJECTIVE To determine whether valproic acid (VPA) influences urinary levels of 15-F2t -isoprostane (15-F2t -IsoP), a marker of oxidative stress, in children. STUDY DESIGN Morning urine samples were collected from children with epilepsy receiving VPA (n = 25), carbamazepine (n = 16), or clobazam (n = 12) for > or = 4 weeks and from age-matched control(More)
Constitutive androstane receptor (CAR) and pregnane X receptor (PXR) are members of the nuclear receptor superfamily. These transcription factors are predominantly expressed in the liver, where they are activated by structurally diverse compounds, including many drugs and endogenous substances. CAR and PXR regulate the expression of a broad range of genes,(More)
Cimetidine is considered to be a general inhibitor of cytochrome P-450 enzymes, but there is indirect evidence that certain cytochrome P-450 enzymes are not inhibited by cimetidine. The purpose of this study was to determine whether cimetidine, when administered in vivo to adult male Wistar rats, selectively inhibits hepatic microsomal cytochrome P-450(More)
trans-Resveratrol (3,5,4'-trihydroxy-trans-stilbene) has been reported to confer chemoprotection against 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenicity in a murine model. A potential mechanism for this effect by trans-resveratrol is inhibition of DMBA-bioactivating cytochrome P450 (CYP) enzymes such as CYP1B1, CYP1A1, and CYP1A2. In the(More)
Valproic acid (2-n-propylpentanoic acid; VPA) has several therapeutic indications, but it is used primarily as an anticonvulsant. VPA is a relatively safe drug, but its use is associated with idiosyncratic hepatotoxicity, which in some cases may lead to fatality. The underlying mechanism responsible for the hepatotoxicity is still not well understood, but(More)
We would like to thank Drs. Hesse and Court for their reading of and comments regarding our recent publication (Chang et al., 2003a). They suggested that an alternative explanation for our data are that differences in mRNA quality among the human liver samples could have resulted in the interindividual variability in CYP2B6, constitutive androstane receptor(More)
The cytochrome P450 enzyme CYP2E1 catalyzes the oxidative metabolism of many solvents and other small organic molecules. A spectrophotometric method is described for determination of CYP2E1 activity by monitoring the formation of p-nitrocatechol from p-nitrophenol by cDNA-expressed CYP2E1 or isolated liver microsomes. The enzymatic product, p-nitrocatechol,(More)