Elimination kinetics and molecular reaction mechanisms of cyclosarin (GF) by an oxime substituted β-cyclodextrin derivative in vitro

Detoxification mechanisms of the chemical warfare agent cyclosarin (GF) in presence of 6-OxP-CD were investigated in detail in in vitro model systems. Most important finding was the preference of 6-Ox-P-CD to eliminate the more toxic (-)-GF. However, elimination of GF enantiomers was dependent on the 6-OxP-CD:GF ratios showing decreasing...

Identification and characterization of the furfural and 5-(hydroxymethyl)furfural degradation pathways of Cupriavidus basilensis HMF14

The toxic fermentation inhibitors in lignocellulosic hydrolysates pose significant problems for the production of second-generation biofuels and biochemicals. Among these inhibitors, 5-(hydroxymethyl) furfural (HMF) and furfural are specifically notorious. In this study, we describe the complete molecular identification and characterization of...

A physiologically based biokinetic (PBBK) model for estragole bioactivation and detoxification in rat

The present study defines a physiologically based biokinetic (PBBK) model for the alkenylbenzene estragole in rat based on in vitro metabolic parameters determined using relevant tissue fractions, in silico derived partition coefficients, and physiological parameters derived from the literature. The model consists of eight compartments including...

Assessment of the multi-mycotoxin-binding efficacy of a carbon/aluminosilicate-based product in an in vitro gastrointestinal model

A laboratory model, set to simulate the in vivo conditions of the porcine gastrointestinal tract, was used to study the small intestinal absorption of several mycotoxins and the effectiveness of Standard Q/FIS (a carbon/aluminosilicate-based product) in reducing mycotoxin absorption when added to multitoxin-contaminated diets. Mycotoxins were...

The FEMA GRAS assessment of hydroxy- and alkoxy-substituted benzyl derivatives used as flavor ingredients

This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the...

The FEMA GRAS assessment of phenethyl alcohol, aldehyde, acid, and related acetals and esters used as flavor ingredients

This publication is the ninth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the Panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to the...

The FEMA GRAS assessment of benzyl derivatives used as flavor ingredients

This publication is the eighth in a series of safety evaluations performed by the Expert Panel of the Flavor and Extract Manufacturers Association (FEMA). In 1993, the panel initiated a comprehensive program to re-evaluate the safety of more than 1700 GRAS flavoring substances under conditions of intended use. Elements that are fundamental to...

Evaluation of the intestinal absorption of deoxynivalenol and nivalenol by an in vitro gastrointestinal model, and the binding efficacy of activated carbon and other adsorbent materials

In vitro screening of 14 adsorbent materials, including some commercial products used to detoxify Fusarium-mycotoxins, were tested in the pH range of 3-8 for deoxynivalenol (DON)- and nivalenol (NIV)-binding ability. Only activated carbon showed to be effective with binding capacities of 35.1 μmol and 8.8 μmol DON and NIV/g adsorbent,...

Disposition of 14C-α-cyclodextrin in germ-free and conventional rats

The absorption, disposition, metabolism, and excretion of uniformly 14C-labeled α-cyclodextrin (14C-α-CD) was examined in four separate experiments with Wistar rats. In Experiment 1, 14C-α-CD (25μCi, 50mg/kg bw) was administered intravenously to four male and four female conventional rats. In Experiment 2, 14C-α-CD (25μCi, 200mg/kg bw) was given...

Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site

Epoxide hydrolases are essential for the processing of epoxide-containing compounds in detoxification or metabolism. The classic epoxide hydrolases have an α/β hydrolase fold and act via a two-step reaction mechanism including an enzyme-substrate intermediate. We report here the structure of the limonene-1,2-epoxide hydrolase from Rhodococcus...

Effects of high fat fish oil and high fat corn oil diets on initiation of AOM-induced colonic aberrant crypt foci in male F344 rats

Modulating effects of high fat fish oil (HFFO) and high fat corn oil (HFCO) diets on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were studied in male F344 rats following 8 weeks of dietary treatment. The incidence of AOM-induced ACF was significantly lower in the proximal colon of rats fed the HFFO diets compared with rats fed...

Recombinant Saccharomyces cerevisiae expressing P450 in artificial digestive systems: A model for biodetoxication in the human digestive environment

The use of genetically engineered microorganisms such as bacteria or yeasts as live vehicles to carry out bioconversion directly in the digestive environment is an important challenge for the development of innovative biodrugs. A system that mimics the human gastrointestinal tract was combined with a computer simulation to evaluate the survival...

Glutathione conjugation as a bioactivation reaction

In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated...

The role of biotransformation in dietary (anti)carcinogenesis

The fact that dietary compounds influence the susceptibility of human beings to cancer, is widely accepted. One of the possible mechanisms that is responsible for these (anti)carcinogenic effects is that dietary constituents may modulate biotransformation enzymes, thereby affecting the (anti)carcinogenic potential of other compounds. This...

A glutathione S-transferase with activity towards cis-1,2- dichloroepoxyethane is involved in isoprene utilization by Rhodococcus sp. strain AD45

Rhodococcus sp. strain AD45 was isolated from an enrichment culture on isoprene (2-methyl-1,3-butadiene). Isoprene-grown cells of strain AD45 oxidized isoprene to 3,4-epoxy-3-methyl-1-butene, cis-1,2-dichloroethene to cis-1,2-dichloroepoxyethane, and trans-1,2-dichloroethene to trans-1,2- dichloroepoxyethane. Isoprene-grown cells also degraded...

Hepatic epoxide concentrations during biotransformation of 1,2- and 1,4- dichlorobenzene: The use of in vitro and in vivo metabolism, kinetics and PB- PK modeling

Glutathione conjugation of the cytostatic drug ifosfamide and the role of human glutathione S-transferases

Development of drug resistance against alkylating cytostatic drugs has been associated with higher intracellular concentrations of glutathione (GSH) and increased expression of glutathione S-transferase (GST) enzymes. Therefore, enhanced detoxification by the glutathione/glutathione S-transferase pathway has been proposed as a major factor in...

In vivo effects of toxic and detoxified endotoxin alone or in combination with muramyl dipeptide on lymphoid and non-lymphoid cells in the spleen of Meth A sarcoma-bearing mice

Chemicals/CAS: Acetylmuramyl-Alanyl-Isoglutamine, 53678-77-6; Acid Phosphatase, EC 3.1.3.2; Antigens, Surface; Antigens, Thy-1; carboxylesterase, EC 3.1.1.1; Carboxylic Ester Hydrolases, EC 3.1.1; Endotoxins; Immunoglobulins, Surface.