Toxin elimination

By applying an extension of the clearance concept 30, 31), in vitro metabolism was used to predict in vivo toxin elimination. Hepatocytes were incubated with 0.5 to 10 pg unlabeled PbTx-3 containing 0.1 pg radiolabeled toxin as tracer. Disappearance of parent compound and the appearance of metabolites were measured by HPLC equipped with a Radiomatic isotope detector. (1.6 nmol/min/g liver)... 

These studies represent the first report of the metabolism of brevetoxins by mammalian systems. PbTx-3 was rapidly cleared from the bloodstream and distributed to the liver, muscle, and gastrointestinal tract. Studies with isolated perfused livers and isolated hepatocytes conflrmed the liver as a site of metabolism and biliary excretion as an important route of toxin elimination. [ H]PbTx-3 was metabolized to several compounds exhibiting increased polarity, one of which appeared to be an epoxide derivative. Whether this compound corresponds to PbTx-6 (the 27,28 epoxide of PbTx-2), to the corresponding epoxide of PbTx-3, or to another structure is unknown. The structures of these metabolites are currently under investigation. 

Phytochemicals, waste and toxin elimination and other fnnetions... 

Umwdtkontaminante Angew Botanik 58 3-10. DeGeoot G and VanHeijst ANP (1988) Toxicoki-netic aspects of thallium poisoning. Methods of treatment by toxin elimination. Sci Total Environ 71 411-418. 

Estimations of the time period required for drug or toxin elimination may be of value in the management of the poisoned patient. If no procedures were used to hasten the elimination of digoxin in this patient, the time taken to reach a safe plasma level of the drug (12.5% of the measured level) is three half-lives, or approximately 7 days. The answer is (B). 

The successful treatment of neonate with severe metabolic intoxication is not possible without securing a vascular catheter (often central venous catheter) that is essential for (1) administering glucose in high concentrations, (2) providing intensive hydration and managing biochemical disturbances, (3) total or partial parenteral feeding, and (4) toxin elimination. 

The liver has been reported to be a major site of residual [ H] T-2 toxin (Matsumoto et al., 1978). It is also an important organ for metabolism (Yoshizawa et al., 1980a) and excretion (Kosuri et al., 1971) of the compound. The slight but insignificant decrease in residual hepatic % when 20% alfalfa was fed may have been due to increased biliary excretion. Kidney is also thought to be a site of T-2 toxin elimination (Kosuri et al., 1971). The... 

Molecular biology is Hkely to have an even greater impact on purification. Molecular cloning of proteins allows the addition of amino acid sequences that can facilitate purification, for example, polyhistidine or polyalanine tails for metal ion, or ion-exchange chromatography. Recent efforts also have employed genetic manipulation to inactivate toxins, eliminating the need for the chemical treatment step. 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

Cellular defense mechanisms against toxins (A multistep mechanism for elimination of toxic metabolites and xenobiotics. It involves various transport, oxidation, and conjugation steps.) are usually divided into several steps as it is visualized on Fig. 3. Organic anion transporting proteins (OATPs) are responsible for the cellular uptake of endogenous compounds and... 

The PSP toxins represent a real challenge to the analytical chemist interested in developing a method for their detection. There are a great variety of closely related toxin structures (Figure 1) and the need exists to determine the level of each individually. They are totally non-volatile and lack any useful UV absorption. These characteristics coupled with the very low levels found in most samples (sub-ppm) eliminates most traditional chromatographic techniques such as GC and HPLC with UVA S detection. However, by the conversion of the toxins to fluorescent derivatives (J), the problem of detection of the toxins is solved. It has been found that the fluorescent technique is highly sensitive and specific for PSP toxins and many of the current analytical methods for the toxins utilize fluorescent detection. With the toxin detection problem solved, the development of a useful HPLC method was possible and somewhat straightforward. 

To further investigate the role of the liver in brevetoxin metabolism, PbTx-3 was studied in the isolated perfused rat liver model (27, 28). Radiolabeled PbTx-3 was added to the reservoir of a recirculating system and allowed to mix thoroughly with the perfusate. Steady-state conditions were reached within 20 min. At steady-state, 55-65% of the delivered PbTx-3 was metabolized and/or extracted by the liver 26% remained in the effluent perfusate. Under a constant liver perfusion rate of 4 ml/min, the measured clearance rate was 0.11 ml/min/g liver. The calculated extraction ratio of 0.55 was in excellent agreement with the in vivo data. Radioactivity in the bile accounted for 7% of the total radiolabel perfused through the liver. PbTx-3 was metabolized and eliminated into bile as parent toxin plus four more-polar metabolites (Figure 3). Preliminary results of samples stained with 4-(p-nitrobenzyl)-pyridine (29) indicated the most polar metabolite was an epoxide. 

Cholera is a serious infection causing epidemics throughout Asia. Although a toxin-mediated disease, largely controlled with replacement of fluid and electrolyte losses, tetracycline has proved effective in eliminating the causative vibrio from the bowel, thereby abbreviating the course of the illness and reducing the total fluid and electrolyte losses. 

Toxoid vaccines. Toxoid vaccines are preparations derived fiom the toxins that are seereted by eertain species of bacteria, hi the manufacture of such vaccines, the toxin is separated fiem the bacteria and treated in a way that eliminates toxicity without eliminating immunogenicity. Formalin (ca. 38% of formaldehyde gas in water) is used for this purpose and consequently the treated toxins are often referred to as formol toxoids. Toxoid vaccines are veiy effective in the prevention of those diseases such as diphtheria and tetanus in which the harmful effects of the infecting bacteria are due to the deleterious action of bacterial toxins on physiology and biochemistry. 

The GIT supplements the kidney in the elimination of wastes and toxins. The P-glycoprotein of enterocytes, which is implicated in multi-drug resistance, plays a critical role. This export carrier exhibits varying responses to the different polyphenols present in green tea (Wang et al, 2002), and is inhibited by one or more components of grapefruit juice (Wagner et al, 2001). It is... 

Patients with previously stable cirrhosis who develop acute encephalopathy often have an identifiable precipitating event that can account for the increased production and/or decreased elimination of these toxins. Infections, variceal hemorrhage, renal insufficiency, electrolyte abnormalities, and increased dietary protein have all been associated with acute development of HE. 

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

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