3alpha,7alpha,12alpha-trihydroxy-5beta-cholan-24-oic (cholic) and 3alpha,7alpha-dihydroxy-5beta-cholan-24-oic (chenodeoxycholic) acids are the predominant hepatic and biliary bile acids of most mammalian species including humans. Cholic and chenodeoxycholic acids are synthesized from cholesterol and accumulate in the liver during cholestasis. Biotransformation by hepatic cytochrome P450 (P450) ...

Methylene chloride is an organic solvent with many industrial uses. Inhalation of methylene chloride fumes can result in toxicity, caused by hepatic biotransformation of methylene chloride to carbon monoxide. A case of acute methylene chloride poisoning is presented, including successful treatment of this patient with the use of hyperbaric oxygenation. The rationale for the use of hyperbaric ox...

N-(4-Fluorophenyl)-N-(1-methylethyl)-2-[[5-(trifluoromethyl)-1,3, 4-thiadiazol-2-yl]oxy]acetamide (FOE 5043) is a new acetanilide-type herbicide undergoing regulatory testing. Previous work in this laboratory suggested that FOE 5043-induced reductions in serum thyroxine (T4) levels were mediated via an extrathyroidal site of action. The possibility that the alterations in circulating T4 levels ...

Microsomal fractions were prepared from the liver of rabbits to investigate the effects of paraquat (methyl viologen) on generation of metabolites of halothane under the optimal aerobic and anaerobic conditions. Halothane (CF3CHClBr) is known to undergo oxidative and reductive biotransformation in the hepatic mixed function oxidase system including cytochrome-P450 reductase and cytochrome P450....

Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated...

The aim of our study was to identify the form(s) of cytochrome P450 responsible for the metabolism of deramciclane, a new anxiolytic drug candidate. The main routes of biotransformation in hepatic microsomes were side chain modification (N-demethylation or total side chain cleavage) and hydroxylation at several points of the molecule. Although several cytochrome P450 forms were involved in the ...

The nuclear receptor peroxisome proliferator-activated receptor (PPAR)α is known primarily as a regulator of fatty acid metabolism, energy balance, and inflammation, but evidence suggests a wider role in regulating the biotransformation of drugs and other lipophilic chemicals. We investigated whether PPARα directly regulates the transcription of cytochrome P450 3A4, the major human drug-metabol...

Sildenafil [SIL (Viagra); Pfizer, New York, NY] is a widely prescribed agent for erectile dysfunction in men older than 65 years. The present study evaluated experimental models to assess age-dependent changes in SIL biotransformation using hepatic microsomes from male rats and mice ranging from 6 weeks to 26 months of age. The role of specific isoforms in the conversion of SIL to its primary c...

The purpose of this investigation was to determine if ethanol enhances the acute toxicity of propoxyphene not only by its central nervous system depressant effect but also by inhibiting the otherwise pronounced presystemic biotransformation of the analgesic. Administration of propoxyphene to adult male rats by injection into either the systemic (jugular vein) or hepatic portal circulation (pylo...