Published in Comprehensive Toxicology
Mycotoxins are secondary metabolites of fungi. Aflatoxins represent one of the most important classes of hepatotoxic mycotoxins known to adversely affect human health. Aflatoxins are the most potent identified mycotoxins and are produced by three fungal species: the common fungal molds Aspergillus flavus and Aspergillus parasiticus, and the rare fu...
Published in Comprehensive Toxicology
Thioacetamide (TA), a centrilobular hepatotoxicant, undergoes a two-step bioactivation mediated by cytochrome P450 (CYP)2E1 to TA sulfoxide (TASO) and further to thioacetamide sulfdioxide (TASO 2), a reactive metabolite that initiates cellular necrosis. Various studies have suggested CYP2E1 to be the specific enzyme responsible for the bioactivatio...
Published in Analytical Biochemistry
A novel method was established for simultaneous quantitation of testosterone (T) and dihydrotestosterone (DHT) in murine tissue and serum samples. Endogenous T and DHT, together with the internal standards 17α-methyl-T and 17α-methyl-DHT, were extracted from tissues and then derivatized by reaction with 2-hydrazino-4-(trifluoromethyl)-pyrimidine (H...
Published in Biochemical Pharmacology
The metabolism of aclidinium bromide, a novel long-acting antimuscarinic drug for the maintenance treatment of chronic obstructive pulmonary disorder, has been investigated in liver microsomes and hepatocytes of mice, rats, rabbits, dogs, and humans. Due to the rapid hydrolysis of this ester compound, two distinct radiolabeled forms of aclidinium w...
Published in Comprehensive Toxicology
Acetaminophen overdose is the most frequent cause of hepatotoxicity and acute liver failure in the United States and many other countries. It is well established that the formation of a reactive metabolite by P450 enzymes is critical for the initiation of the injury process. Although the reactive metabolite is detoxified by reaction with glutathion...
Published in Expert opinion on drug metabolism & toxicology
Cytochrome P450 enzymes comprise a superfamily of heme monooxygenases that are of considerable interest for the: i) synthesis of novel drugs and drug metabolites; ii) targeted cancer gene therapy; iii) biosensor design; and iv) bioremediation. However, their applications are limited because cytochrome P450, especially mammalian P450 enzymes, show a...
Published in Molecular Biology
Chronic obstructive pulmonary disease (COPD) is a multifactorial respiratory disorder. Members of the cytochrome P450 family catalyze oxidative metabolism of exogenous chemicals and activate their substrates into reactive intermediates that may initiate lung injury. The frequencies of CYP1B1 and CYP2F1 polymorphic markers were determined in healthy...
Published in Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry
A method for direct registration of CYP51b1 (sterol-14α-demethylase) activity with coumarin derivatives as substrate has been proposed. Determination of catalytic activity of this enzyme with 7-aminocoumarin-4-acetic acid (ACAC) is based on registration of the increase of fluorescence (λexcitation = 360 nm and λemission = 435 nm) at 30°C. In the mo...
Published in Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry
Cytochrome P450 is an important class of enzymes metabolizing numerous drugs. The composition and activity of these enzymes determine distribution of drug in the body, their pharmacological and toxic effects. Thus, prediction of the fate of compounds in the body is required at early stages of the development of new drugs. Different isoforms of cyto...
Published in Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry
Recent advances in nanotechnologies resulted in significant progress in the development of sensor systems based on nanocomposite materials. This review summarizes own and literature data on the sensor system based on hemoproteins which are functionally important for medicine. Special attention is paid to the electrochemical nanobiosensors and princ...
