Knowledge of strain differences in drug metabolism is important for the selection of animals for pharmacokinetic, pharmacodynamic, and toxicological studies. Hepatic microsomes from Sprague-Dawley (SD) and Brown Norway (BN) rats had 300-fold higher diazepam p-hydroxylation activity than Dark Agouti (DA) and Wistar (W) rats at a low diazepam concentration (3 microM). Kinetic studies indicated th...

tidepressants that are widely used clinically. As shown in Fig. 1, IMI is oxidized by cytochrome P450 (CYP) mainly via two pathways: side-chain N-demethylation and aromatic ring 2-hydroxylation, forming DMI and 2-hydroxyimipramine (2OH-IMI), respectively. DMI and 2-OH-IMI further undergo 2-hydroxylation and N-demethylation, respectively, forming 2-hydroxy-DMI as the common metabolite (Fig. 1). ...

In classic cholic acid biosynthesis, a series of ring modifications of cholesterol precede side chain cleavage and yield 5beta-cholestane-3alpha, 7alpha, 12alpha-triol. Side chain reactions of the triol then proceed either by the mitochondrial 27-hydroxylation pathway or by the microsomal 25-hydroxylation pathway. We have developed specific and precise assay methods to measure the activities of...

Roxithromycin has been shown to be a relatively weak inhibitor of cytochrome P450 (P450 or CYP)-dependent drug oxidations, compared with troleandomycin. The potential for roxithromycin and its major metabolites found in human urine [namely the decladinosyl derivative (M1), O-dealkyl derivative (M2), and N-demethyl derivative (M3)] to inhibit testosterone 6b-hydroxylation after metabolic activat...

HUMAN LIVER ALDEHYDE OXIDASE (ALDEHYDE: O(2) oxidoreductase, EC 1.2.3.1) has been purified 60-fold and some of its properties studied. Like aldehyde oxidase from other mammalian species, human liver aldehyde oxidase is an enzyme with dual substrate specificity, possessing the ability to catalyze not only the oxidation of aldehydes to the corresponding carboxylic acids, but also the hydroxylatio...

DFT studies show that the rebound mechanism for MnO(tpp)(Cl)-catalyzed C-H hydroxylation is favored for spin states with oxyl character.

Polychlorinated Biphenyl-Induced Alteration of Biologic Parameters in the Rat. BRUCKNER, J. V., KHANNA, K. L. AND CORNISH, H. H. (1974). Toxicol. Appl. Phurmacol. 2-8, 189-199, Aroclor 1242, a commercial polychlorinated biphenyl (PCB) mixture, was administered ip to rats for 10 weeks. Principal findings included: loss of body weight; hepatic and renal damage, with some animals exhibiting renal ...

N-Hydroxylation and mutagenic activation of heterocyclic aromatic amines from protein pyrolysis products were studied in rat liver microsomes and nuclei, rat hepatocytes and various species of purified cytochrome P-450. These mutagenic amines include Trp-P-2 (3-amino-1-methyl-5H-pyrido[4,3-b]indole), Trp-P-1 (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole), Glu-P-1 (2-amino-6-methyldipyrido-[1,2-a...