Detoxification and Cleansing Programs

Detox Diet Basics

Detox Diet Basics

Our internal organs, the colon, liver and intestines, help our bodies eliminate toxic and harmful  matter from our bloodstreams and tissues. Often, our systems become overloaded with waste. The very air we breathe, and all of its pollutants, build up in our bodies. Today’s over processed foods and environmental pollutants can easily overwhelm our delicate systems and cause toxic matter to build up in our bodies.

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7 Day Raw Detox

The 7 Day Raw Detox is a vegan 7 day detox which means no consumption of processed foods (unless processed by you) no cooked food of any kind and nothing that originates from a living creature including any animals or insects. This includes no alcohol, coffee, meat, eggs, cheese, dairy, sugar, cereal, bread pasta, rice, packet food or anything perserved through a cooking method of any kind. You will be provided with all the recipes, shopping lists, templates, meal planners and more you need to organize your shopping and food for your detox. You will also be invited to join a Vip Support Group on Facebook with other Detox participants with daily motivation and support by the detox crew.

7 Day Raw Detox Summary

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I usually find books written on this category hard to understand and full of jargon. But the author was capable of presenting advanced techniques in an extremely easy to understand language.

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Peptides Bound to LPS

Investigations of the interactions between LPS (or lipid A) and oligopeptides were motivated by the finding that polymyxin B (PmB, mo-KTK'-cyclo-fK'K'fLK'K'Tl mo methyl octanoate K' diaminobutyric acid (Dab) f D-Phe the cycle is closed between the side-chain of Dab 4 and the main chain of Thr 10, Fig. 2), a cyclic, cationic peptide antibiotic, binds to lipid A 16 with an apparent dissociation constant in the jiM range 17 and neutralizes its pathogenicity. Unfortunately, PmB is toxic and can not be used for therapy. A series of peptides designed to mimic the primary and secondary structure of PmB was synthesized and tested for binding and detoxification of LPS lipid A 18 , 19 . Other peptides that bind and detoxify LPS are derived from proteins that bind LPS, e.g. LBP 20 , 21 , limulus anti-LPS factor (LALF) 21 , 22 , bactericidal permeability-increasing protein (BPI) 21 , 23 and heparin binding protein (HBP) 24 .

Toxic Agents Drug Overdose Poisons Contrast Media

The first line of treatment of poisons and drug overdoses taken by mouth is an attempt to prevent absorption of these agents from the gastrointestinal tract. Once intestinal absorption has occurred, detoxification, blockade of toxic effects and elimination by metabolism or excretion can be considered as a second line of defense. The kidneys are perfused with plasma at the rate of about 36 liters hour, and about 7 liters of this plasma will be filtered per hour. Thus, an absorbed toxic agent in the blood will traverse the kidney very frequently.

Metabolism and Excretion of Toxicants

Leupeptin Plant

Thus, the liver is the richest source of enzymes for metabolizing toxicants, but there is ample evidence that enzyme systems are ubiquitous, which can be rationalized on the basis of the importance of such enzymes in detoxifying various compounds. Intestinal microflora plays an important role in the biotransformation of One of the unique facets of toxicant metabolism is that even though structures of these potentially toxic products, be they natural or synthetic, are so tremendously varied, the body seems to have evolved detoxifying processes that can cope with almost any of the many different compounds. Animals possess enzymes that can metabolize drugs, pesticides, secondary plant metabolites, and synthetic compounds as defense mechanisms, which are likely because of evolution in response to selective pressures for protection against many naturally occurring toxic products. There are two categories of animal enzyme systems (1) those for the transformation of normal endogenous...

Interactions between Saprotrophic Basidiomycetes and Bacteria

Bacteria play an important role in the functioning of lignocellulose-degrading basidiomycetes. They can have a negative effect on fungal growth and activity as they are potential competitors for low-molecular weight compounds released by extracellular fungal enzymes. There are also some indications of bacterial mycophagy. On the other hand, basidiomycetes may benefit from the presence of bacteria, in particular with respect to nitrogen supply and detoxification of mycotoxic compounds.

Cpg Island Hypermethylation Changes During Prostate Cancer Initiation And Progression

Prostate Examine

In 1994, Lee et al. demonstrated that hypermethylation of CGI sequences within the regulatory region of GSTP1, which encodes the pi-class glutathione S-transferase (GST) enzyme, is an extremely frequent feature of human prostate cancer (49, 50). Since that initial study, numerous groups have independently corroborated these findings using a wide array of techniques applied to numerous prostate cancer DNA sources, including prostatectomy specimens, prostate autopsy specimens, prostate biopsy specimens, prostate secretions, and various bodily fluids from prostate cancer patients. Furthermore, GSTP1 CGI hypermethylation appears to be an extremely specific finding for prostate cancer as it is not characteristic of normal prostates or benign prostatic hyperplasia. The GST enzymes catalyze the detoxification of carcinogens and reactive chemical species via the conjugation of glutathione. It has been hypothesized that loss of this detoxification agent in prostate cells might make them...

Hepatic Encephalopathy Is A Disorder Of Astrocyte Function Resulting In A N E U R O P S Y C H I At R I C Syndrome

Astrocyte Reactive Hyperplasia

Ginated, and a prominent nucleolus is often observed. Lipofuscin deposits may be present, and the amount of the astrocyte-specific protein glial fibrillary acidic protein (see Chapter 2) is decreased. Neurons appear structurally normal. All the foregoing histopathological changes have been reproduced in vitro by acutely or chronically applying ammonium chloride to primary astrocyte cultures. As mentioned earlier, detoxification of ammonium is an ATP-requiring, astrocyte-specific reaction catalyzed by glutamine synthase (see Fig. 3.12). It is therefore not surprising that excess ammonia perturbs energy metabolism indeed, ammonia stimulates glycolysis (McKhann and Tower, 1961) whereas it inhibits TCA cycle activity (Muntz and Hurwitz, 1951). In addition, ammonia markedly decreases the glycogen content of astrocytes. A key function of astrocytes is to remove synapti-cally released glutamate. A large proportion of glutamate is transformed to glutamine through an energy-requiring process...

Mutualistic Interactions

Bacteria that detoxify fungal cell membrane disrupting compounds produced by bacterial pathogens of fruit bodies (see above) may also be considered as mutualists of basidiomycetes. Tsukamoto et al. (2002) isolated several tolaasin-detoxifying strains from wild Agaricales. Perhaps the presence of tolaasin-detoxifying strains on wild mushrooms explains why P. tolaasii is much more frequently isolated from cultivated mushrooms than from wild ones (Bessette, 1984). More detailed investigations are needed to understand the nutritional requirements of the antagonists of P. tolaasii. If they are preferentially selected by the fungus, for example via a resistance to antibacterial compounds and are growing on fungal exudates, this would be true mutualism.

Resistance In Nonpest Species

The ability of insect predators and parasitoids to develop pesticide resistance would be of enormous benefit to pest management strategies that are chemically dependent. Although pyrethroid and organophosphate resistance has been documented in predatory mites (e.g., Typhlodromus pyri in orchards and Amblyseius womersleyi in tea fields) and hymenopterous parasitoids (e.g., Aphytis holoxanthus in orchards and Anisopteromalus calandrae in grain stores), reports of insecticide-resistant beneficial species from the field are far rarer than they are for pest species. Reporting bias aside, the most likely reasons for this are the difficulty in host location when both natural enemy and host are under selection pressure and, in comparison with herbivorous species, the possibility that the enzyme systems of predators and parasites are less well adapted to detoxify xenobiotics.

Examples of developments in plant GE

An alternative approach but still using A. tumefaciens has been to transfer the genes for mammalian cytochrome P450 monooxygenases, known to be involved in the detoxification (and activation) of many xenobiotics including pesticides, into tobacco plants. These transgenics displayed resistance to two herbicides, chlortoluron and chlorsulphuron (Yordanova, Gorinova and Atanassov 2001). Chapter 7 mentioned the genetic modification of a poplar to enable mercury to be removed from the soil and converted to a form able to be released to the atmosphere. This process is termed 'phytovolatilisation' (Rugh et al. 1998). The modification required a gene to be constructed, styled on the bacterial merA gene, by making a copy reflecting the codon bias found in plants using PCR technique. The mer A gene is one of a cluster of genes involved in bacterial detoxification of mercury, and is the one coding for the enzyme, mercuric ion reductase, which converts mercury from an ionic to a volatile form....

Sample Adulteration in Urine DOA Testing

The instant DOA testing procedures are instituted, opposing forces are at work to develop methods to avoid detection of drug use. Initially, common household chemicals such as laundry bleach, table salt, toilet-bowl cleaner, hand soap, and vinegar were used. More recently, a variety of products became commercially available, which can be ordered through Internet sites and tollfree telephone numbers. Commercially available adulteration products can be classified into two broad categories. The first category consists of specific fluids or tablets, which when taken along with plenty of water, serve to flush out drugs and metabolites, resulting in diluted urine and reduced concentrations of drugs or metabolites. Examples of products in this category include Absolute Detox XXL drink, Absolute Carbo Drinks, Ready Clean Drug Detox Drink, Fast Flush Capsules, and Ready Clean Gel Capsules. All products are available from Internet sites. Root Clean is a hair-cleansing system targeting drug...

Eukaryotic Cell Structure And Function

In eukaryotes, the ribosomes line a folded membrane structure called the endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm. ERs serve as channels to transport newly synthesized substances within a cell. The part studded with ribosomes, called the rough ER, is responsible for the synthesis of proteins, including enzymes. Another portion of the ER, the smooth ER, lacks ribosomes. The smooth ER is associated with synthesis of lipids and the detoxification of lipid-soluble toxins. The liver has abundant smooth ER. It is the location of the enzyme complex cytochrome P450 system, which is responsible for much of the liver's detoxification activity as well as other biotransformation functions (see Section 18.5) Other vesicles, including lysosomes, remain in the cytoplasm. Lysosomes contain enzymes that can digest particles taken in by endocytosis or, interestingly, can be used by the cell to commit suicide, when the cell is damaged or otherwise unneeded. Other...

Inherited Peripheral Neuropathies

FIGURE 1.19 The glutamate-glutamine cycle is an example of a complex mechanism that involves an active coupling of neurotransmitter metabolism between neurons and astrocytes. The systems of exchange of glutamine, glutamate, GABA, and ammonia between neurons and astrocytes are highly integrated. The postulated detoxification of ammonia and inactivation of glutamate and GABA by astrocytes are consistent with the exclusive localization of glutamine synthetase in the astroglial compartment. Gln, glutamine. FIGURE 1.19 The glutamate-glutamine cycle is an example of a complex mechanism that involves an active coupling of neurotransmitter metabolism between neurons and astrocytes. The systems of exchange of glutamine, glutamate, GABA, and ammonia between neurons and astrocytes are highly integrated. The postulated detoxification of ammonia and inactivation of glutamate and GABA by astrocytes are consistent with the exclusive localization of glutamine synthetase in the astroglial compartment....

Natural Enemy Conservation Concept of Natural Control

Before 1947, few synthetic pesticides were used in crops. Most available materials were stomach poisons based on heavy metals such as lead and arsenic, which kill only if eaten. Some botanical extracts, such as rotenone and pyrethrum, both of which quickly degrade in the environment, were also used. After World War II, a business revolution occurred when it became recognized that a variety of compounds that could be artificially synthesized in laboratories were highly effective in killing insects by mere physical contact. Beginning with DDT in 1947, many types of chemicals were marketed to kill insects. One of the undesirable consequences of this change in farming practice was the mass destruction of beneficial insects in crops, resulting in a substantial decrease in natural control. Indeed, insecticides often killed natural enemies more efficiently than they killed the target pest. This unintended consequence was due to the smaller body size, greater relative surface area, and lower...

Gender Ethnicracial And Life Span Considerations

Some patients may be misusing and abusing psychoactive drugs through ignorance. Others may have begun using them as part of a physician-prescribed treatment regimen and then became addicted. If the individual is unable to give a history because of overdose, friends or family members may provide needed information and clothing can be checked for drug paraphernalia. Elicit a history of previous detoxification treatments, effectiveness, length of recovery, and what influenced a return to drug usage.

Effects on Particular Organs or Organ Systems

As mentioned above, particular toxins will tend to target particular organs or organ systems. The liver and the kidney are common targets of toxic activity because of their role in detoxification and their large blood flow. The skin and eyes, lungs, and digestive tract are vulnerable to the more reactive toxicants, as they are the sites of first entry to the organism. The nervous system has both unique protection and vulnerability. Liver The liver receives almost all the venous blood flow prior to its return to the heart and lungs. All of the blood from the stomach and intestines go directly to the liver. Thus, substances absorbed in the GI tract may be biotransformed before reaching other organs. Although the liver detoxifies most compounds, some are converted to more toxic forms. As the generator of most of the bioactivated compounds (see Section 18.5), the liver is also the site of first and most concentrated contact. The liver is the main site of toxic damage for a number of...

TABLE 123 Phenolic Substances

Thiosulfate plays a key role in detoxification of cyanide. Thiosulfate originates from sulfate metabolism. More than 800 phenolic substances are known in plants. Such compounds contribute to the bitter taste, flavor, and color of foods. Table 12.3 lists some classes of phenolic substances. Most of the phenolic substances are devoid of acute toxicity. Methods are available to detoxify them.

Origins And Breadth Of Resistance

Cross-resistance patterns are inherently difficult to predict in advance, because mechanisms based on both increased detoxification and altered target sites can differ substantially in their specificity. The most commonly encountered patterns of cross-resistance tend to be limited to compounds in the same chemical class (equivalent to the term side-resistance as used by parasitologists). However, even these patterns can be very idiosyncratic. For example, organophosphate resistance based on increased detoxification or target-site alteration can be broad ranging across this group or highly specific to a few chemicals with particular structural similarities. The breadth of target-site resistance to pyrethroids in houseflies is also dependent on the resistance allele present. The kdr allele itself affects almost all compounds in this class to a similar extent ( 10-fold resistance), whereas resistance due to the more potent super-kdr allele is highly dependent on the alcohol moiety of...

Diet and biotransformation

The biotransformation of a toxic compound usually, but not always, results in detoxification. It can, however, lead to the metabolic activation of foreign compounds. The effect of dietary constituents on the metabolism of foreign compounds has been the subject of intensive study for many years. More than two decades ago, the term toxicodietetics was coined for the study of dietary factors in the alterations of toxicity a term that was perhaps ahead of its time. There are a multitude of dietary factors that can affect toxicity. Dietary factors can be associated with the exposure situation, ranging from factors such as palat-ability of the food to the physical volume or rate of food ingestion. Dietary factors can be responsible for producing changes in the body composition, physiological and biochemical functions, and nutritional status of subjects. These factors, and others, can have marked influences on the toxicity of substances. For example, it is customary to fast laboratory...

Individual Variability

Young animals are typically 1.5 to 10 times as sensitive to toxins as adults, possibly due to underdeveloped immunity or detoxification mechanisms. Malathion is about 28 times more toxic to newborn rats than to adults. However, this is not always the case. DDT is about 20 times less toxic to newborns, and Dieldrin was about 4.5 times less toxic. The young may absorb differently, and their blood-brain barrier is less efficient.

Udpglucuronosyltranferase 1a1

UDP-glucoronosyltransferases are enzymes responsible for detoxification and elimination of various metabolites and drugs. These enzymes also catalyze the inactivation of irinotecan (CPT-11), an analog of the alkaloid campto-thecin. CPT-11 is clinically used for the treatment of refractory and advanced colorectal cancers. Dose-limiting toxicities are diarrhea and pancytopenia. CPT-11 is metabolized to its active product, SN-38, by the enzyme carboxylesterase 2. As depicted in Fig. 3, UGT1A1 is responsible for the inactivation of SN-38, the most relevant metabolite of CPT-11, to the glucuronide of SN-38. CPT-11 can also be directly inactivated by formation of the inactive oxidation product, aminopenthan carboxylic acid (APC). Responsible for this step are cytochromes P450 3A4 and 3A5, as shown in Fig. 3. However, the formation of the SN-38 glucuronide is the

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All three studies (29-31) observed expression of genes associated with detoxification and antioxidant properties that were highly expressed in a set of adenocarcinomas and mostly in squamous cell tumors. These genes include glutathione peroxidase, glutathione S-transferase, carboxylesterase, and aldo-keto reductase. Their presence in squamous cell lung cancers, which are usually centrally located in the lung and associated with tobacco smoking, may reflect a response by the bronchial epithelium to carcinogenic insults.

Sage Uses In Human Genome Mining And Annotation

Recently, hierarchical clustering was used to analyze SAGE data, comparing normal lung epithelial cells and non-small cell lung cancers. One hundred fifteen transcripts were identified that clearly distinguished both groups (i.e., normal and tumors), and furthermore, it was possible to differentiate non-small cell lung cancer histological subtypes. Adenocarcinomas were characterized by high level of expression of small airway-associated or immunologically related proteins, and the p53 target genes p21 (CDKN1A) and 14-3-3 were consistently underexpressed. Squamous cell carcinomas were characterized by overexpression of genes involved in detoxification or antioxidation. These observations were validated by real-time PCR analyses in larger numbers of samples, importantly indicating that an analysis of a limited number of SAGE libraries was sufficient to provide information significant for defining tumor-specific molecular signatures, which could then be extrapolated to a larger scale...

Issues Related to Toxicity

The severity of chemical-induced toxicity is a function of three major determinants (1) the intrinsic toxic property of a chemical (2) its local concentration at a particular organ and (3) the ability of the host defense systems to detoxify the chemical and cope with chemical injuries. The first determinant is embedded in the chemical structure and considered as an intrinsic toxic property of a chemical.8

Herbicide Resistant Crops

Bioremediation is the use of organisms to break down and thereby detoxify dangerous chemicals in the environment. Plants and microorganisms are used as bioremediators. The technology can take advantage of a natural metabolic pathway or genetically modify an organism to have a particular toxic appetite.

Deiodination of Iodothyronines

A high degree of similarities has been demonstrated between the structures of the deiodinases and the reactions they catalyze 50 . Yet, there are also important differences in their catalytic properties (table 3 fig. 4). D1 catalyzes both outer and inner ring deiodination while D2 only outer ring and D3 inner ring deiodination, respectively 52 . In addition to deiodination, iodothyronines are metabolized by conjugation of the phenolic hydroxyl group with sulphate or glucoronic acid (so-called phase II detoxification reactions) 53, 54 . The purpose of this is to increase the water solubility of the substrates and thereby to

Biological Removal Biotransformation and Biosorption of Metal Ions from Contaminated Wastewater

Whereas solid organic and inorganic material in wastewater or sludge can be removed by sedimentation, soluble organic pollutants and xenobiotics should be eliminated from the aqueous environment by microbial mineralization or anaerobic degradation to gaseous products, with a varying portion (5 -50 ) being used as substrates for bacterial growth. Most of the inorganic components present in wastewater are soluble and are ionized. Trace amounts of many cations (e.g., Na+, K+, Ca2+, Fe2+, Ni2+, Co2+, Mn2+, Zn2+, etc.) and anions (e.g., PO3-, Cl-, S2-) are essential micronutrients for bacterial growth. Other cations such as ammonia may also be required for bacterial growth, but the surplus amount must be oxidized to nitrate, and the nitrate denitrified to gaseous nitrogen, for N elimination from wastewater. Under anaerobic conditions sulfate is reduced to sulfide, low amounts of which are required for growth of bacteria. The sulfide not required for growth is toxic for bacteria if present...

Practical Toxicity Issues

In broad terms, type-A metals are less toxic than type-B, but this is only a generalisation and a number of other factors exert an influence in real-life situations. Passive uptake by plants is a two-stage process, beginning with an initial binding onto the cell wall followed by diffusion into the cell itself, along a concentration gradient. As a result, those cations which readily associate with particulates are accumulated more easily than those which do not. In addition, the presence of chelating ligands may affect the bio-availability and thus, the resultant toxicity of metals. Whereas some metal-organic complexes (Cu-EDTA for example) can detoxify certain metals, lipophilic organometallic complexes can increase uptake and thereby the functional toxic effect observed.

What are the Effects on Gene Expression by Different Tocopherols

An early study suggested that vitamin E affects the expression of the aryl hydrocarbon hy-droxylase gene, a P450 oxygenase (Pi-450) involved in the detoxification of polynuclear aromatic hydrocarbons and in the disposition of certain drugs 164 . Since a-tocopherol inhibits PKC activity, and PKC ultimately regulates the phosphorylation of several transcription factors, it was postulated that several genes may be regulated by tocopherols.

Oral ingestion studies

The bioactivity of a toxicant ingested varies with the frequency, presence of food, and the makeup of the food, such as amount of purified sugar, fiber, high protein, or high fat. The different pH conditions of the gastrointestinal tract affect the ionization of weak organic acids and bases. Following absorption in the gastrointestinal tract, the bioactive chemical is translocated to either the lymphatic system or the portal circulation. The portal circulation directs the chemicals to the liver, and many of the chemicals are excreted by the liver as bile. Because the bile empties back into the intestine, a cycle involving translocation of the chemical from the gastrointestinal tract to the liver and via the bile back to the intestine occurs. This cycle is known as enterohepatic circulation. Ingestion of chemicals from the gastrointestinal tract and enterohepatic cycle exposes the liver to those concentrations of the agent that would not be obtained by other exposure routes, such as...

Mechanistic Aspect Of Chemoprevention

The recent progress in molecular biology of cancer has identified key components of the intracellular signaling network, especially protein kinases and transcription factors, that function abnormally during the course of cellular transformation and malignancy. In response to carcinogenic stimuli, the intracellular signaling network becomes disrupted, thereby favoring premalignant and malignant transformation of cells. Therefore, the modulation of inappropriate cell signaling cascades might be a realistic approach in achieving chemoprevention. Mechanistically, the process of carcinogenesis can be prevented in both the initiation and promotion stages by targeting signal transduction pathways involved in carcinogen detoxification, cellular proliferation, inflammation, apoptosis, and angiogenesis (Figure 1.1) 5,8 .

Control Of Bile Acid Transport And Metabolism

An important mechanism toward controlling bile acid levels within cells is to adjust the cellular uptake or efflux of bile acids by regulating the expression and or activity of uptake and efflux proteins, as discussed in detail below. It should be noted, however, that additional mechanisms are also operational in preventing intracellular bile acid concentrations from reaching toxic levels. One such mechanism is to regulate the de novo synthesis of bile acids according to the existing intracellular bile acid content. To reduce bile acid synthesis, the expression levels of the key CYP enzymes involved in de novo bile acid synthesis (i.e., CYP7A1, CYP8B1, and CYP27A1) are suppressed.42 Furthermore, expression levels of several phase II enzymes that in addition to their role in drug detoxification may convert bile acids into less toxic and more hydrophilic derivatives are induced in response to elevated levels of bile acids.43 These metabolizing enzymes include uridine 5'...

The Genome of Dictyostelium discoideum Adam Kuspa and William F Loomis

The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. One of the initial surprises was the remarkably large number of genes that are shared with plants, animals, and fungi that must have been present in their common progenitor over a billion years ago. The genome encodes a total of about 10,300 proteins including protein families involved in cytoskeletal control, posttranslational protein modification, detoxification, secondary metabolism, cell adhesion, and signal transduction. The genome has a higher proportion of homopolymeric tracts and simple sequence repeats, such as CAA than most other genomes. Triplet repeats in translated regions produce the highest known proportion of polyglutamine tracts in any known proteome. Phylogenetic analyses based on complete proteomes confirm that the amoebozoa are a sister group to the...

Adulteration Techniques and Products

Presently, the use of household products to defeat drug testing (6) has been mostly replaced by commercial products that are widely available via the Internet, mail-order through advertisements in such counter-culture, promarijuana-use magazines as High Times and Cannabis Culture, or purchase at head shops and the GNC vitamin store chain. To bypass the law, these products are frequently labeled as detoxification (detox) products and often come with a disclaimer that they are not intended for use on lawfully administered drug tests and are to be used in accordance with all federal and state laws.

Nuclear Receptors As Transcriptional Regulators Of Bile Acid Homeostasis

Receptor that typically utilizes drugs and xenobiotics as its ligands.66 In response to these ligands, PXR induces the expression of genes encoding proteins involved in drug detoxification and elimination pathways. In addition to xenobiotics, certain bile acids, such as the highly toxic LCA, can serve as agonistic ligands for PXR.67-68 Indeed, activation of PXR can protect mouse livers against LCA-mediated injury.67 Doubleknockout mice lacking both FXR and PXR exhibit more severe disturbances of bile acid metabolism than mice lacking only one of the nuclear receptors, demonstrating that both contribute to bile acid homeostasis.69 PXR is a master regulator of the gene encoding the CYP3A4 enzyme,70 which, in addition to its role in detoxifying xeno-biotics, also metabolizes bile acids to less toxic and more easily excreted derivatives. Thus, by being both activators of the CYP3A4 gene and substrates of the CYP3A4 enzyme, bile acids can initiate a hepatoprotective feedforward loop via...

Molecular Mechanisms In The Generation And Propagation Of Aberrant Dna Methylation Patterns In Prostate Cancer

Conjugated oxidant species that would then have to be transported out of the cell or metabolized further into inert compounds. Surprisingly, however, the GSTP1 expressing LNCaP clones exhibited less clonogenic survival than the control LNCaP cells (94). In a similar experiment, Diah et al. overexpressed GSTP1 and or MRP1, a glutathione-conjugated toxin active transporter, in MCF7 breast cancer cells, which normally do not express either of these proteins. They then treated these cells and MCF7 wild type controls with the toxin 1-chloro-2,4-dinitrobenzene (CDNB), and found that a) MCF7 cells overexpressing MRP1 alone had three to four fold increased resistance to CDNB cytotoxicity associated with a 10 fold increase in efflux of the glutathione conjugate of CDNB as compared to wild type MCF7 cells, b) MCF7 cells overexpressing both MRP1 and GSTP1 showed increased formation and a commensurate increase in efflux of the glutathione conjugate of CDNB and increased resistance to short-term...

Intracellular Redox State And Oligodendrocyte Survival

One of our particular interests has been in using glutathione pro-drugs as a means of modulating intracellular redox state, with N-acetyl-L-cysteine (NAC) being of particular utility. NAC is one of several compounds that can be used to augment intracellular levels of glutathione, the major scavenger of reactive oxi-dative intermediates present in all eukaryotic forms of life 70 . Glutathione is generally required to protect cells against damage by oxidants and is able to reduce and thereby detoxify these potentially damaging chemical species. NAC enters cells readily and replenishes intracellular cysteine required to produce glutathione, thus leading to an increase in glutathione levels. NAC itself also may react with

Conclusions And Questions To Address In Future Studies

Phytate might influence oxidative stress by mechanisms independent of its hydroxyl radical inhibiting characteristics. It may alter cell signaling pathways as proposed by Shamsuddin 1,22,23 , or it may influence the activity and expression of key enzymes in the antioxidant defense system. Singh and Singh 24 have reported that phytate given by oral gavage to lactating mice for 21 days led to increases in the activity of glutathione-S-transferase, (GST), the protein levels of cytochromes b5 and P-450, as well as the content of acid-soluble sulfhydryl groups in the livers of both the dams and their suckling pups. The GST family includes the non-selenium glutathione peroxidase, an important component of the cell's antioxidant defense machinery, and an enzyme that is upregulated in response to antioxidant nutrient deficiency 25 . Thus, phytate may also contribute to antioxidant defense by increasing the activity of key enzymes that detoxify ROS. Future research should also explore multiple...

Recycling Of Intramitochondrial Coash

As well as recycling of intramitochondrial CoASH by citrate synthase, there are other routes via which CoASH can be recycled. These are indicated in Table 1. Firstly, the carnitine acyltransferases, coupled with carnitine-acylcarnitine translocase, can export acyl groups, thus recycling intramitochondrial CoASH. Secondly, acyl-CoA hydrolases can hydrolyse the thioester link directly. They have been shown to be active in recycling CoASH from medium and short chain acyl-CoAs during inhibition by hypo-glycin metabolites.35,38,39 As well as having a high Kmapp for acyl-CoA esters, medium acyl-CoA hydrolase is inhibited by CoASH, thus further limiting their action. Another important route both of detoxification and recycling of CoASH, is glycine conjugation by the matrix enzyme acyl-CoA glycine-N-acyltransferase, which has maximal activity towards aromatic acyl-CoA esters and is the route of appearance of hippuric acid.43 5 Finally, intramitochondrial acyl-CoA synthases are reversible so...

Natural Microbial Bioremediators

Another environmental disaster being treated with natural bioremedi-ation is the pollution of the Hudson River in New York with polychlori-nated biphenyls (PCBs). General Electric Corporation deposited these compounds along a 40-mile stretch of the river between 1947 and 1977. PCBs were used to manufacture hydraulic fluids, capacitors, pigments, transformers, and electrical equipment. PCBs come in 209 different and interconverting forms, and the toxicity of a particular PCB depends upon the number of chlorine atoms it includes. Debate rages over whether it is better to remove and bury the most contaminated sediments, or to allow natural bacteria in the river to detoxify the PCBs. The bioremediation of the Hudson River is occurring in three stages. First, buried anaerobic bacteria strip off chlorines. In the water column, aerobic bacteria cleave the two organic rings of the PCBs. Finally, other microorganisms degrade the dechlorinated, broken rings into carbon dioxide, water, and...

Pharmacogenetics Of Drugmetabolizing Enzymes

Detoxification of environmental constituents including dietary components, no selection pressure is put on the conservation of functionally active genes subjects lacking one or several types of these genes usually have a normal physiological phenotype. The major part of the interethnic differences in the genetic constitution of these genes is a result of incidental mutations in the genes, amplified in certain areas because of population expansion. The lack of endogenous function of the gene products has thus allowed this extensive heterogeneity with respect to allelic distributions in different parts of the world.

Distribution And Storage

The major sites of storage for toxins are (1) bound to plasma proteins, (2) the liver and kidneys, and (3) adipose tissue. Plasma proteins form complexes with many toxicants, serving to solubilize and transport them. The effect of protein binding depends on how the proteins compete with processes that detoxify or excrete them. If they give up the toxicants readily, they may help to transport them to the detoxification site. If, on the other hand, protein binding is relatively strong, it may sequester the toxins away from detoxification. Toxins are often concentrated in the liver or kidneys, possibly due to their role in detoxifying and excreting them. They contain their own binding proteins. An example is metallothionein, which figures in cadmium storage and in the transfer of cadmium from the liver to the kidney. Toxins absorbed in the stomach and intestines must pass through the liver before reaching other parts of the body, thus giving that organ a chance

Membrane Bioreactors

Membrane Bio Reactor

The membrane bioreactor has proved its suitability as an efficient system for degradation of recalcitrant compounds and significantly higher biomass concentrations and utilisation rates are routinely achieved than in corresponding alternative treatment systems. In common with most operational, rather than experimental, biological detoxification processes, not all of the contaminants present in the effluent are typically completely converted into carbon dioxide and water, a certain percentage being turned into metabolic byproducts instead, though this can amount to less than 5 in a well-managed bioreactor system. Part of this involves the gradual and controlled introduction of novel wastewater elements, to ensure that acclimatisation is maximised and any potential tendency for 'shock loadings' avoided. This is a clear example of the value of permitting optimised microbial adaptation to the individual application.

Endocrine disrupters

As an aside, glucuronidation is not confined to hormones but is a process used to detoxify a number of drugs, toxins and carcinogens in the liver. The enzyme catalysing this process is induced in response to prolonged exposure to the toxin thus imparting increased tolerance or even resistance to the chemical.

KXH kXH HCHO

Methyl groups are transferred from one of two methyl donor substrates, S-adenosyl-methione (SAM) or N5-methyltetrahydrofolic acid. Methylation occurs with a variety of methyl-acceptor substrates, including proteins, nucleic acids, and phospholipids. Interestingly, methyl conjugates are generally less water soluble than the parent compound. However, methylation is generally considered a detoxification reaction. Processes that produce a one-electron reduction of oxygen produce a more reactive radical, the superoxide anion. The superoxide anion can be formed from oxygen by an enzyme in white blood cells and other enzymes or certain toxic agents. ROS can be eliminated by the enzymes superoxide dismutases, which convert two molecules of superoxide to one molecule each of hydrogen peroxide and oxygen (Figure 9.9). Hydrogen peroxide is another ROS that can be formed by some two-electron transfer reactions. As illustrated in Figure 9.9, hydrogen peroxide is detoxified by glutathione...

Fat Body

The insect fat body is a mesodermal tissue composed of a meshwork of loose lobes suspended in the hemocoel and bathed in the insect hemolymph. The tissue is composed primarily of vacuolated rounded or polyhedral cells called adipocytes or trophocytes, which commonly harbor stored inclusions of proteins, lipids, and glycogen. In certain insect species, mycetocytes (cells containing symbiontic microorganisms) and urocytes (cells containing nitrogenous waste product in the form of uric acid) are present. The fat body is also associated with connective tissue and various blood cell types. Being a major biosynthetic and storage organ in insects, the insect fat body is equivalent to the vertebrate liver. It is the prime location of intermediary metabolism and detoxification processes, as well as storage and excretion of glycogen, lipids, and proteins. Storage of reserves is characteristic of the larval fat body cells. Such reserves are subsequently used for metamorphosis in holometabolous...

Metabolic Functions

As in vertebrates, the oxidative metabolism is mediated via the tricarboxylic acid (TCA) cycle and the electron transport enzyme systems. The fat body contains enzymes mediating the gluconeogenesis process as well as enzymatic systems with a detoxification role to manage harmful endogenous metabolites and toxic xenobiotic compounds. Detoxifying enzyme systems include microsomal mixed function oxidases, in which the cytochrome P450 is predominant, various hydrolytic enzymes (esterases, phosphoesterases), and conjugating systems.

Repairing the Damage

DNA is constantly being damaged, and it is constantly being repaired as well. It is only when the damage is not repaired that a mutation can lead to cancer or cell death. The DNA repair enzymes can recognize damaged nucleotides and remove and replace them. The human liver contains a large number of enzymes whose role is to detoxify toxic compounds, mutagenic or otherwise, by chemically reacting them. However, in some cases these enzymes (called cytochrome P450s) actually create mutagens during the course of these reactions. Such bioactivation may be a significant source of mutagens. see also Carcinogens Chromosomal Aberrations DNA Repair Muller, Hermann Mutagenesis Mutation.

The Cyp Induction

Induction is defined as the increase in the amount and activity of a drug metabolizing enzyme that generally requires more than acute exposure to the inducing agent.177 Induction of CYPs and other ADME enzymes may cause reduction in therapeutic concentration, and thereby the efficacy of comedications. For example, by this mechanism rifam-picin caused acute transplant rejection in patients treated with cyclo-sporine, presumably because of induction of the clearance of cyclosporine.178,179 Also, induction may create an undesirable imbalance between detoxification and activation as a result of increased formation of reactive metabolite leading to an increase in risk of metabolite induced toxicity.180,181 Unlike CYP inhibition, which is almost immediate, CYP induction is a less immediate process. It takes time to reach a higher steady-state enzyme level as a result of a new balance between

Pathophysiology

Cellular detoxification, a property apparently not shared by MRP6, and has a capacity to confer chemotherapy resistance to the cells. While the exact pathomechanisms leading to abnormalities in the elastic fiber network of the target organs are poorly understood, deposition of calcium is considered merely a secondary change that can occur after trauma to elastic fibers. As a result of calcification, fragmentation or disorganization of elastic fibers in the midreticular dermis and the medium-sized arteries and veins as well as the fractures in Bruch's membrane behind the retina occurs. In the skin, this leads to inelasticity, loss of recoil, and subsequent sagging of the skin. In the eye, neovascularization occurs at sites of fracture due to calcium deposits. These newly formed vessels are fragile and often rupture with trauma. In the arteries, alteration of elastic fibers leads to calcification of the elastic media and later the intima, which facilitates atherosclerotic peripheral...

Membrane network

The intracellular network of membrane-enclosed cisternae, vesicles and membranous organelles occupies about one-half of the volume of the cytoplasmic or cytosol compartment. Numerous membranous organelles that reside in the cytosol, among them the mitochondria, which are involved in energy metabolism, and microbodies, which participate in detoxification reactions, are omitted from Fig. 1 and are not further discussed because they have only a peripheral role in virus infections. The predominant structures enclosed by membranes are the endoplasmic reticulum (ER) and Golgi apparatus, which are transiently interconnected with each other and the plasma membrane by transport vesicles. A specialized continuum of the ER are the cisternae enclosed by the The ER provides a surface for enzymes such as those that catalyze the detoxification of drugs prominent in the liver, and as an attachment surface for ion pumps such as those for sequestering Ca2+ in the sarcoplasmic reticulum of muscle....

Gender and age

With age, our ability to metabolize foreign compounds reduces. Xenobiotic metabolism is low or absent in the fetus and neonates, develops rapidly after birth, and is highest in early adulthood. Before birth, the capacity for handling metabolism of foreign compounds is through the mother's metabolism. Clusters of different enzymes seem to develop rapidly during development periods, birth, weaning, and puberty. Many of the age-related differences, particularly between the young and old, can be explained by quantitative differences in detoxification processes. There is also a difference in hepatic and renal clearances of toxicants between newborn and adult animals. The necessity for dose adjustment is well recognized in pediatrics and in certain situations wherein patients have impaired kidneys.

Nat And Disease

Because of the role of acetylation in the metabolic activation and detoxification of arylamine and heterocy-clic carcinogens, acetylator status and cancer risk have been widely investigated. Unlike the relatively rare but highly penetrant genes involved in familial cancers, those genes responsible for metabolic polymorphisms have low penetrance and cause only a moderate increase in cancer risk. Nevertheless, their widespread occurrence in the general population suggests they are a significant contributor to individual risk. However, few diseases have consistently demonstrated a relationship between pheno-type and risk. For example, several studies have implicated the rapid phenotype as an increased risk factor for colon cancer, 15-17 whereas others have been unable to confirm this finding. 18-20 Geographical differences, ethnicity, lack of study power, dietary differences, and differences in other risk factors between study groups have been suggested as reasons for variable results...

Species

As one ascends through the different taxonomic levels, it can be assumed for comparison that the more closely related taxonomically the surrogate species, the more likely it is that the test will be predictive for humans. Species and strain differences in susceptibility to a toxic compound are generally greater than litter mate differences. Biological diversity is often taken advantage of when seeking to discover new pesticides or chemotherapeutic agents, such as the ability of the host to detoxify a compound compared with that of a pest or parasite, i.e., comparative or selective toxicity.

Cadmium

After absorption, cadmium binds to the protein metallothionein in cells of the intestinal tract wall and in the liver. Metallothionein is a key protein that contributes to the homeostasis of essential zinc and copper and in the detoxification of heavy metals. If people do not eat foods that contain enough iron or other nutrients, they are likely to take up more cadmium than the usual from their food. The general population and people living near hazardous waste sites may eat or drink cadmium in food, dust, or water.

Dpd Inhibitors

While the three others act as DPD inhibitors (competitive inhibition). Details on the clinical development on these compounds will be given in other chapters in this book. We will insist on the main characteristics of these DPD inhibitors. With 5-ethynyluracil pretreatment, the biovailability of 5-FU becomes complete and thus renal clearance becomes the main source of drug elimination with significant correlations having been shown between 5-FU clearance and creatinine clearance (35). A consequence could be that dosage reductions would need to be made in patients with reduced renal function who are candidates for 5-ethynyluracil and 5-FU combined treatment. Competitive inhibitors of DPD activity are also part of the new products UFT, Si, and BOF-A2. UFT contains uracil and tegafur in a 4 1 ratio and Si includes 5-chloro-2,4-dihydropyrimidine (CDHP) in combination with tegafur and potassium oxonate. BOF-A2 is an oral prodrug of 5-FU and 3-cyano-2,6-dihydropyrimidine (CNDP). CNDP is a...

Aflatoxin

Aflatoxins are heat stable and easily transformed to toxic products. Treatment with ammonia reduces and inactivates aflatoxins. Lactic fermentation at pH 4.0 results in the conversion of AFB1 to AFB2a, which is less toxic. Other environmental conditions, such as the presence of organic acid, also irreversibly convert AFB1 to aflatoxicol B, which is 18 times less toxic than AFB1. Detoxification results in the opening of the lactone ring (see Figure 13.2) and can be monitored by reduced fluorescence.

Dioxins

The paradox becomes more complicated when one considers that several nutrients have a profound effect on mercury and methyl mercury toxicity (selenium, zinc, vitamins C and E). For more than 30 years, the protective effects of selenium against mercury have been known. Many marine organisms that have high tissue levels of mercury also have high tissue levels of selenium, or a mercury-to-selenium tissue ratio of 1 1 stoichiometrically. Thus, the apparent survival of certain species in the conditions of mercury intoxication may be related to a detoxification mechanism involving interactions between mercury and selenium. An interaction between the two elements may involve sequestering and neutralizing the toxic effects of either ionic mercury or organic mercury. Selenite (SeO3) may act to both demethylate methyl mercury and form a molecular detoxification product of selenite and mercuric

Carcinogenesis

Another type of epigenetic carcinogen is the cocarcinogens These increase the concentration of an initiator by affecting absorption, biotransformation, or detoxification. For example, they may decrease detoxification by inhibiting enzymes or depleting detoxification substrates such as glutathione. Ferric oxide and asbestos may facilitate cellular uptake of genotoxics.

Abcc1

Bronchial Drug Transporter Localisation

Some studies suggested an involvement of Abccl in the efflux of substances from the brain into blood,184 whereas others did not.185'186 In human and murine kidney, ABCCl Abccl is present in the epithelial cells of the loop of Henle and urinary collecting ducts.176'187 In colon, highest ABCC1 levels are found in the Paneth cells of the crypts, but not in the epithelial cells.187 This ABCC1 tissue distribution and localization pattern, which is almost mutually exclusive to that of ABCC2 (Section 11.5.2), indicates that ABCC1 has an important function in the detoxification of substances from those cells and tissues that do not express ABCC2. Subsequent to its first demonstration in the canalicular membrane of rat and human hepatocytes,8'41'156 ABCC2 Abcc2 was also identified in the apical membrane of polarized cells of rat and human kidney proximal tubules,188'189 human small intestine,190'191 colon,141'191 gallbladder,192 bronchi,141'191 and placenta.180'193 The exclusive apical...