Xenobiotics

Specific regions in the rodent larynx exhibit cellular changes in response to inhaled xenobiotics. These regions include the base of the epiglottis, ventral pouch, and medial surfaces of the vocal processes of the arytenoid cartilages. There are interspecies differences among laboratory rodents in the microscopic anatomy of these sensitive areas of the laryngeal mucosa. In CRL:CD strain Sprague-Dawley rats, the

Xenobiotic solutions of different concentrations were analyzed by TLC method before and after passing trough the column with adsorbent M and compared with adsorption on the active charcoal. The efficiency of adsorption on adsorbent M was higher, compared to active charcoal. The best adsorption, in the value 90 - 100%, have shown certain organochlorine and organophosphorus pesticides, that were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven in vivo, when solutions of tested xenobiotics before adsorption have caused death of experimental animals, and after the adsorption on adsorbent M, all treated animals have survived and had just mild symptoms of poisoning.

The xenobiotic transporters are among the most important constituents of detoxification system in living organisms. Breast cancer resistance protein (BCRP/ABCG2) is one of the major transporters involved in the efflux of xenobiotics. To understand its role in chemotherapeutic and multidrug resistance, it is crucial to establish the determinants of its substrate specificity, which obviously is of high relevance for successful therapy of many diseases. This article summarizes the current knowledge about the substrate preferences of BCRP. We overview the factors which determine its activity, inhibition and substrate recognition, focusing on the structural features of the transporter. BCRP substrate specificity is quite low as it interacts with a spectrum of substances with only a few common features: hydrophobic and aromatic regions, possibly a flat conformation and the metal ion-, oxygen- and nitrogen-containing functionalities, most of which may be the donors/acceptors of H-bonds. Se...

Metabolic processes have to be regulated tightly to prevent waste of energy and to ensure sufficient detoxification. Most anabolic processes operate in a timely manner when energy intake is the highest, while catabolism takes place in energy spending periods. Endobiotic and xenobiotic metabolism are therefore under circadian control. Circadian regulation is mediated through the suprachiasmatic nucleus (SCN), a master autonomous oscillator of the brain. Although many peripheral organs have their own oscillators, the SCN is important in orchestrating and entraining organs according to the environmental light cues. However, light is not the only signal for entrainment of internal clocks. For endobiotic and xenobitoic detoxification pathways, the food composition and intake regime are equally important. The rhythm of the liver as an organ where the major metabolic pathways intersect depends on SCN signals, signals from endocrine tissues, and, importantly, the type and time of feeding or xenobiotics ingestion. Several enzymes are involved in detoxification processes. Phase I is composed mainly of cytochromes P450, which are regulated by nuclear receptors. Phase II enzymes modify the phase I metabolites, while phase III includes membrane transporters responsible for the elimination of modified xenobiotics. Phases I-III of drug metabolism are under strong circadian regulation, starting with the drug-sensing nuclear receptors and ending with drug transporters. Disturbed circadian regualtion (jet-lag, shift work, and dysfunction of core clock genes) leads to changed periods of activity, sleep disorders, disturbed glucose homeostasis, breast or colon cancer, and metabolic syndrome. As many xenobiotics influence the circadian rhythm of the liver, bad drug administration timing can worsen the above listed effects. This review will cover the major hepatic circadian regulation of endogenous and xenobiotic metabolic pathways and will provide examples of how good timing of drug administration can change drug failure to treatment success.

Pesticides are extensively used in agriculture as a part of pest control strategies. Owing to their xenobiotics characteristics, pesticides may adversely affect the proliferation of beneficial soil microorganisms and their associated biotransformation in the soil. Inactivation of nitrogen‐fixing and phosphorus‐solubilizing microorganisms is observed in pesticide‐contaminated soils. Recent studies show that some pesticides disturb molecular interactions between plants and N‐fixing rhizobacteria

Inhibitory analysis of top-down control: new keys to studying eutrophication, algal blooms, and water self-purification. – Hydrobiologia. 2002, vol. 469, p. 117-129; http://www.scribd.com/doc/52598579/;
**
It is the first article in which the new experimental results of the author were analyzed to give a new fresh insight into ecological mechanisms of eutrophication and abnormal increase in phytoplankton. Also, a new insight into how ecosystem runs water self-purification.
A fundamentally new approach and methodology to study top-down control in ecosystems: the first introduction of what the author calls ‘inhibitory analysis’. The paper presented a new insight in understanding that a decrease in activity of filter-feeders are part of the causes and mechanisms of eutrophication and algal blooms. The paper shows how to identify and measure this new factor which stimulates those negative phenomena.

**
Main discoveries made by the same author:
Публикации того же автора. Основные результаты. Main Results: http://www.scribd.com/doc/59437439/;
On the author / Об авторе (С.А.О.):
http://www.famous-scientists.ru/3732/;

Flavonoids from fruits and vegetables probably reduce risks of diseases associated with oxidative stress, including cancer. Apples contain significant amounts of flavonoids with antioxidative potential. The objectives of this study were to investigate such compounds for properties associated with reduction of cancer risks. We report herein that apple flavonoids from an apple extract (AE) inhibit colon cancer cell growth and significantly modulate expression of genes related to xenobiotic metabolism. HT29 cells were treated with AE at concentrations delivering 5–50 µM of one of the major ingredients, phloridzin (“phloridzin-equivalents,” Ph.E), to the cell culture medium, with a synthetic flavonoid mixture mimicking the composition of the AE or with 5–100 µM individual flavonoids. HT29 cell growth was inhibited by the complex extract and by the mixture. HT29 cells were treated with nontoxic doses of the AE (30 µM, Ph.E) and after 24 h total RNA was isolated to elucidate patterns of gene expression using a human cDNA-microarray (SuperArray®) spotted with 96 genes of drug metabolism. Treatment with AE resulted in an upregulation of several genes (GSTP1, GSSTT2, MGST2, CYCP4F3, CHST5, CHST6, and CHST7) and downregulation of EPHX1, in comparison to the medium controls. The enhanced transcriptional activity of GSTP1 and GSTT2 genes was confirmed with real-time qRT-PCR. On the basis of the pattern of differential gene expression found here, we conclude that apple flavonoids modulate toxicological defense against colon cancer risk factors. In addition to the inhibition of tumor cell proliferation, this could be a mechanism of cancer risk reduction. © 2005 Wiley-Liss, Inc.