Removal Of Xenobiotics Research Articles

Study of P450 function using gene knockout and transgenic mice

The xenobiotic-metabolizing P450s have been extensively studied for their ability to metabolize endogenous and exogenous chemicals. The latter include drugs and dietary and environmentally derived toxicants and carcinogens. These enzymes also metabolize endogenous steroids and fatty acids. P450s are thought to be required for efficient removal of most xenobiotics from the body and to be responsible for the hazardous effects of toxicants and carcinogens based on their ability to convert chemicals to electrophilic metabolites that can cause cellular damage and gene mutations. P450 catalytic activities have been extensively studied in vitro and in cell culture, yielding considerable information on their mechanisms of catalysis, substrate specificities, and metabolic products. Targeted gene disruption has been used to determine the roles of P450s in intact animals and their contributions to the mechanisms of toxicity and carcinogenesis. The P450s chosen for study, CYP1A1, CYP1B1, CYP1A2, and CYP2E1, are conserved in mammals and are known to metabolize most toxicants and chemical carcinogens. Mice lacking expression of these enzymes do not differ from wild-type mice, indicating that these P450s are not required for development and physiological homeostasis. However, the P450 null mice have altered responses to the toxic and carcinogenic effects of chemicals as compared with wild-type mice. These studies establish that P450s mediate the adverse effects of drugs and dietary, environmental, and industrial chemicals and serve to validate molecular epidemiology studies that seek to determine links between P450 polymorphisms and susceptibility to chemically associated diseases. More recently, P450 humanized mice have been produced.

Engineering of membrane biosorption

Membrane biosorption is a new integrated process for xenobiotics removal from a water environment. The mathematical model has been presented in the paper based on biosorption equilibrium and kinetics as well as relevant mass balances of the integrated system. To achieve steady-state conditions the biosorbent has to be renewed on the membrane surface prior to its saturation with the solute. This can be done either by periodical backflushing in the case of supercritical flux when the biosorbent forms the cake or by continuous renewal with cross flow (turbulence and shear stresses) during subcritical conditions. The engineering aspects of the process design and optimisation are discussed in the paper. The permeate flux has to be adjusted to actual kinetics of the sorption. The choice of optimal time intervals for batch mode with backflushing and proper hydrodynamical conditions for continuous cross-flow mode were also demonstrated. Membrane biosorption is especially feasible for removal of diluted components with high retention. The naturally occurring microorganisms may be applied as a sorbent. Membrane biosorption is a cheap and efficient method of xenobiotics separation and therefore may be applied for environmental protection purposes.

Enhanced Removal of Xenobiotics by Helophytes

The aromatic xenobiotics 2,6-dimethylphenol, 4-chlorophenol and naphthalene were removed using hydroponic cultures of Carex gracilis and Juncus effusus and using sand-bed reactors planted with Carex gracilis and Juncus effusus, respectively, under batch and flow-through conditions. Concentrations of 20 mg/l organic pollutant in the case of 4-chlorophenol, about 30 mg/l naphthalene and 50 mg/l2,6-dimethylphenol were efficiently eliminated over periods of up to six months. Plant cultures were found to achieve a better removal rate than plant-less systems. In the systems investigated, organic xenobiotics are thought to be mainly degraded by bacteria in the rhizosphere. The plants were not observed to suffer any damage when exposed to the above-mentioned pollutant concentrations. Indeed, plants responded to 2,6-dimethylphenol with better growth, implying that the plants benefited from the xenobiotic. However, whereas Carex gracilis plants exposed to more than 10 mg/l 4-chlorophenol initially died off, after a few weeks' of exposure up to 10 mg/l, they tolerated up to 30 mg/l 4-chlorophenol.

Xenobiotics removal from polluted water by a multifunctional constructed wetland

Removal efficiencies on xenobiotics from polluted water in a twin-shaped constructed wetland consisting of a vertical flow chamber with the crop plant Colocasia esculenta L. Schott and a reverse vertical flow one with Ischaemum aristatum var. glaucum Honda, were assessed by chemical analysis and bioassays. After a four-month period of application, removal efficiencies of the applied pesticides parathion and omethoate were 100% with no detectable parathion and omethoate in the effluent. For the applied herbicides, the decontamination was less efficient with removal efficiencies of 36% and 0% for 4-chloro-2-methyl-phenoxyacetic acid and dicamba, respectively. As shown by toxicity assay with duckweed Lemna minor L., growth retardation may occur if the water treated for herbicide removal is used in irrigation of sensitive cultivars in agriculture or horticulture. In contrast to I. aristatum var. glaucum Honda, the crop C. esculenta L. Schott has a high yield in biomass production as a valuable source of renewable energy.

Effects of Bergenin, the Major Constituent of Mallotus japonicus against D-Galactosamine-Induced Hepatotoxicity in Rats

The hepatoprotective effects of bergenin, a major constituent of Mallotus japonicus, were evaluated against D-galactosamine (GalN)-induced liver damage in rats. Bergenin (50, 100 and 200 mg/kg) was given orally once daily for 7 successive days and then GalN 400 mg/kg was injected intraperitoneally to rats at 24 and 96 h after the final administration of bergenin. Pretreatment with bergenin reduced the increased enzyme activities of alanine/aspartate aminotransferase, sorbitol dehydrogenase, γ-glutamyltransferase and the elevated level of malondialdehyde induced by GalN. Bergenin restored the decreased hepatic contents of glutathione as well as the decreased activities of glutathione S-transferase and glutathione reductase by GalN towards normalization, suggesting that the hepatoprotective effects of bergenin may consist in maintaining adequate levels of hepatic glutathione for the removal of xenobiotics. The present results indicate that bergenin has hepatoprotective effects against GalN-induced hepatotoxicity in rats.

Promiscuous regulator of xenobiotic removal

The transcription factor SXR mediates drug, xenobiotic and steroid induction of a major drug–metabolizing enzyme. Drugs such as paclitaxel (Taxol) can bind and activate this transcription factor and therefore regulate their own metabolism and efflux from cells. Manipulation of this pathway might lead to new ways to improve therapeutic efficacy and to minimize toxicity ( 584–590 ).

The ability of different plant species to remove polycyclic aromatic hydrocarbons and polychlorinated biphenyls from incubation media

The ability of in vitro cultured cells of black nightshade, wheat, barley, soybean, tomato, mulberry and birch to grow in the presence of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) and to metabolise them was compared. No correlation was found between the resistance of the plants and removal of xenobiotics. Up to 20% of PCBs and over 90% of PAHs were removed by wheat cells from nutrient media in two weeks.

Humic acids: Their detergent qualities and potential uses in pollution remediation

Humic acids are amphiphilic species whose behavior in aqueous solution suggests that they form pseudomicelles–aggregates akin to the micelles familiar from synthetic surfactant chemistry. It is thought that humic pseudomicelles can be formed by both intramolecular coiling and intermolecular association, depending on the molecular weight, structural characteristics, and polydispersity of the humic acid in question. The process does not feature a critical micelle concentration. Experimental evidence indicates that metal ions enhance the detergent character of dissolved humic acid by facilitating the coiling and folding of the polymer chains. A recently conceived alternative model suggests that humic acids consist of relatively small subunits that associate through weak molecular interactions. This view appears to run counter to certain experimental observations, but deserves careful attention. The strong association between metal ions and solid humic acid makes it possible to use an inexpensive commercial grade for the decontamination of polluted water. A continuous elution process through a column packed with humic acid allows for the removal of both heavy metals and organic xenobiotics from aqueous solution.

Nuclear magnetic resonance in environmental engineering: principles and applications.

This paper gives an introduction to nuclear magnetic resonance spectroscopy (NMR) and magnetic resonance imaging (MRI) in relation to applications in the field of environmental science and engineering. The underlying principles of high resolution solution and solid state NMR, relaxation time measurements and imaging are presented. Then, the use of NMR is illustrated and reviewed in studies of biodegradation and biotransformation of soluble and solid organic matter, removal of nutrients and xenobiotics, fate of heavy metal ions, and transport processes in bioreactor systems.

Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics.

Besides renal excretion, hepatic metabolism and biliary excretion are the major pathways involved in the removal of xenobiotics. Recently, for many endogenous and exogenous compounds (including drugs), it has been reported that carrier-mediated transport contributes to hepatic uptake and/or biliary excretion. In particular, primary active transport mechanisms have been shown to be responsible for the biliary excretion of anticancer drugs, endogenous bile acids and organic anions including glutathione and glucuronic acid conjugates. Primary active excretion into bile means the positive removal of xenobiotics from the body, and this elimination process is now designated as "Phase III" (T. Ishikawa, Trends Biochem. Sci., 17, 1992) in the detoxification mechanisms for xenobiotics in addition to Phase I by P-450 and Phase II by conjugation. The transporters, which have been called P-glycoprotein (MDR), multidrug resistance related protein (MRP) and GS-X pump and which are believed to be involved in the primary active pumping of xenobiotics from the cells, are now known as the ATP-binding cassette (ABC) transporters. In this review, we first describe the HMG-CoA reductase inhibitor, pravastatin, as a typical case of a carrier-mediated active transport system that contributes to the liver-specific distribution in the body. Regarding biliary excretion, we have summarized recent results suggesting the possible contribution of the ABC transporters to the biliary excretion of xenobiotics. We also focus on the multiplicities in both hepatic uptake and biliary excretion mechanisms. Analyzing these multiplicities in transport is necessary not only from a biochemical point of view, but also for our understanding of the physiological adaptability of the living body in terms of the removal (detoxification) of xenobiotics. Clarification of these transport mechanism may provide important information for studying the pharmacokinetics of new therapeutic drugs and furthermore, leads to the development of the drug delivery systems.

Phase-3 Detoxification in the Liver: Biliary Excretion of small molecules and peptides by primary active transport mechanisms

Recently, for many endogenous and exogenous compounds(including drugs), it has been reported that carrier-mediated primary active transport contributes to biliary excretion. Compounds known to be excreted by this mechanism are anticancer drugs, endogenous bile acids and organic anions including glutathione and glucuronic anid conjugates. Primary active excretion into bile means the positive removal of xenobiotics from the body, and the elimination process is now designated as “Phase III” (T.Ishikawa, Trends Biochem.Sci., 17, 1992) in the detoxification mechanisms for xenobiotics in addition to Phase I by P-450 and Phase II by conjugation. There exist multiplicities in the biliary excretion mechanisms. Clarification of these multiplicities in transport is necessary not just from a biochemical point of view, but for our understanding of the physiological adaptability of the living body in terms of the removal (detoxification) of xenobiotics. This may provide a lot of important informations for studying the pharmacokinetics of new drugs. In this presentation, I would like to summarize the latest experimental results on carrier-mediated biliary excretion systems and the multiplicities in the biliary excretion of xenobiotics, including small peptides.

Sequential degradation of chlorophenols by photolytic and microbial treatment

Using the radiolabeled model pollutants 2,4-dichlorophenol (DCP) and 2,4,5-trichlorophenol (TCP) the authors demonstrated that the brief UV (300-nm) photolysis greatly facilitates the removal of the two chlorophenols from sewage through accelerated mineralization and binding of polar products. The addition of 0.1 M H/sub 2/O/sub 2/ strongly accelerated the photolysis process resulting in the half-lives of 1.68 and 0.87 min for DCP and TCP, respectively. In natural sunlight, half-lives of the chlorophenols were less than 1 day when H/sub 2/O/sub 2/ was present. During 4 days of incubation in activated sewage sludge, only 3% of unphotolyzed DCP and 1% of unphotolyzed TCP were mineralized. Mineralization rose to 79 and 59%, respectively, after photolysis in the presence of H/sub 2/O/sub 2/. Photolysis without H/sub 2/O/sub 2/ resulted in removal of chlorophenols from solution chiefly by binding. Increased mineralization and binding were observed also upon incubation of photolyzed chlorophenols in soil. Disruption of carbon-halogen bonds by brief photolysis followed by traditional biological effluent treatment offers an alternative to activated charcoal treatment for removal of xenobiotics from industrial effluents.

Influence of adipocyte triglyceride on the partition of 2,2',4,4',5,5'-hexabromobiphenyl between 3T3L1 adipocytes and surrounding pseudoblood.

Removal from adipose tissue is an important first step in ultimate removal of many lipophilic xenobiotics from the body. This study concerned the elucidation of mechanisms by which hexabromobiphenyl (HBB) was deposited in and removed from adipocytes. Adipocytes derived from the 3T3L1 cell line of mouse fibroblasts were used to conduct studies in vitro. Results support the idea that HBB enters the 3T3L1 adipocyte via passive diffusion. A plot of the velocity of uptake versus concentration was linear, the uptake of HBB does not appear to be energy dependent, and structurally similar biphenyls did not cause an inhibition of uptake. A linear relationship between the quantities of triglyceride and HBB in the cells was found during both uptake of HBB in lipogenesis and removal of HBB in lipolysis (r greater than 0.98). This supports the contention that the quantity of triglyceride in the cells has a strong influence on the movement of HBB between adipocytes and surrounding pseudoblood. Evidence has been presented that is consistent with the hypothesis that HBB moves freely across the adipocyte membrane and is sequestered in either cells or medium according to its relative solubility in these compartments. Methods to increase the removal of HBB from adipocytes have been proposed.

Developments in biotechnology of relevance to drinking water preparation

This paper discusses strategies to increase the feasibility of microorganisms for the removal of toxic xenobiotics from waste water and drinking water. Based on the principles of adaptational mutations and genetic exchange of catabolic activities, it becomes possible to select and engineer microorganisms that are suitable for the degradation of recalcitrant compounds. The detailed biochemical knowledge that is required for this is now rapidly evolving, and especially for the degradation of chlorinated organics several detoxifying dehalogenation mechanisms have been studied in detail. The feasibility of specialized bacteria for waste and water treatment will be dependent on the possibility to obtain stable performance and maintenance in treatment systems.