من انا

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الرياض, Saudi Arabia
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الثلاثاء، 31 يناير، 2012

toxins


Identification of toxins

A

Bio-toxins

The term "bio-toxin" is sometimes used to confirm the biological origin. Toxins produced by microorganisms are important virulence determinants responsible for microbial pathogenicity and/or evasion of the host immune response.

Bio-toxins vary greatly in purpose and mechanism, and can be highly complex (the venom of the cone snail contains dozens of small proteins, each targeting a specific nerve channel of receptor), or relatively small protein.

Bio-toxins in nature have two primary functions:

1.Predation (spider, snake, scorpion, jellyfish, wasp).

2.Defense (bee, ant, termite, honeybee, wasp, poison dart frog).


Some of the more well known types of bio-toxins include:

1.Necrotoxins cause necrosis (i.e., death) in the cells they encounter and destroy all types of tissues. Necrotoxins spread through the bloodstream. In humans, skin and muscle tissues are most sensitive to necrotoxins.

2.Neurotoxins primarily affect the nervous systems of animals. Organisms that possess neurotoxins include:

Cytotoxins are toxic at the level of individual cells, either in a non-specific fashion or only in certain types of living cells:

Apitoxin, the honey bee venom

Mycotoxins are toxins produced by fungi. They are a common source of toxins in grains and other foods.


Factors affecting the toxicity

Poisoning potential is usually determined more by the multitude of related factors than by the actual toxicity of the poison.

1.Exposure-related factors.

2.Biological factors.

3.Chemical factors.

      All the previous factors regulate absorption, metabolism, elimination, and thus, influence the clinical consequences.

I- Exposure-related factors

The dose is a primary concern; however, the exact intake of poison is seldom known. Duration and frequency of exposure are important. The route of exposure affects absorption, translocation, and perhaps metabolic pathways. The time of administration relative to periods of stress, food intake, etc, may also be a factor, e.g., following ingestion of some toxicants, emesis may occur if the stomach is empty, but if partly filled, the toxicant is retained and poisoning can occur.


Environmental factors, such as temperature, humidity, and barometric pressure, affect rates of consumption and even the occurrence of some toxic agents. Many mycotoxins and poisonous plants are correlated with seasonal or climatic changes, e.g., the ischemic effects of ergot poisoning are more often observed during the winter cold, and plant nitrate levels are affected by rainfall amounts.

II- Biological factors

Various species and strains within species react differently to a particular poison because of variations in absorption, metabolism, or elimination. Functional differences in species may also affect the likelihood of poisoning (e.g., species unable to vomit can be intoxicated with a lower dose of some agents).The age and size of the animal are primary factors in poisoning. Metabolism and translocation of xenobiotic agents are compromised by the underdeveloped microsomal enzyme system in young animals; membrane permeability and hepatic and renal clearance capabilities vary with age, species, and health.


Nutritional and dietary factors, hormonal and health status, organ pathology, stress, and sex all affect poisoning. Nutritional factors may directly affect the toxin (i.e. by altering absorption) or indirectly affect the metabolic processes or availability of receptor sites. (The copper-molybdenum-sulfate interaction is an example of both).


III- Chemical factors

The chemical nature of a toxicant determines solubility, which in turn influences absorption. Non-polar or lipid-soluble substances tend to be more readily absorbed than polar or ionized substances. The vehicle or carrier of the toxic compound also affects its availability for absorption. Generally, as absorption is delayed, toxicity decreases. Flavoring agents affect palatability, and thus the amount ingested.

Endotoxins

Endotoxins are compounds found in the cell walls of Gram negative bacteria. These compounds help to form a semi-permeable membrane which is designed to protect bacteria from threats. Once the bacteria die, the endotoxins are released, and many of these toxins cause health problems in people, animals, and other organisms, hence the “toxin” in their name.

Classically, endotoxins cause inflammatory processes, which can lead to fever, vomiting, diarrhea, changes in white blood cell counts, and high blood pressure.



Many endotoxins come in the form of lipopolysaccharides, although other chemical compounds may appear as well. These toxins can become a serious problem in the wake of a bacterial infection, or when bacteria contaminate medications, food, and lab samples, because the toxins tend to resist heat and many other sterilization methods. As a result, when someone consumes a product contaminated with bacteria which contain endotoxins, they can become sick.

Exotoxins

An exotoxin is a toxin excreted by a microorganism, like bacteria, fungi, algae, and protozoa. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell.

Most exotoxins can be destroyed by heating. They may exert their effect locally or produce systemic effects. Well-known exotoxins include the botulinum toxin produced by Clostridium botulinum and the Corynebacterium diphtheriae exotoxin, which is produced during life-threatening symptoms of diphtheria.

Exotoxins are susceptible to antibodies produced by the immune system, but many exotoxins are so toxic that they may be fatal to the host before the immune system has a chance to mount defenses against it.


Comparison of Exotoxins and Endotoxins

Exotoxins

Produced by both Gram-positive and Gram-negative bacteria.

Released from cell.

Protein.

Many types of exotoxins based on structure and function.

Heat labile.

Specific receptors on
host target cells.

Specific effects in host.

Toxoids can be made
by treating with formalin.     

Endotoxins

Produced only by
Gram-negative bacteria .

Integral part of cell wall.

Lipid A of lipopolysaccharides.

Only one type of endotoxins.

Heat stable. Diverse range of host cells and systems affected.

Diverse range of effects in host.

Toxoids cannot be made.    

Phytotoxins

Phytotoxin refers to a substance produced by a plant that is toxic or a substance that is toxic to the plant. Many substances produced by plants are secondary metabolites and are the by-products of primary physiological processes. Some examples of phytotoxins are alkaloids, terpenes, phenolics, herbicides and substances produced by bacteria.

Fungal phytotoxins

1.Tentoxin: Tentoxin is produced by the fungus Alternaria alternata (previously called A. tenuis), which causes spots and chlorosis (Fig. 3) in plants of many species. Seedlings with more than one-third of their leaf area chlorotic die, and those with less chlorosis are much less vigorous than healthy plants. Tentoxin is a cyclic tetrapeptide that binds to and inactivates a protein (chloroplast-coupling factor) involved in energy transfer into chloroplasts. The toxin also inhibits the light-dependent phosphorylation of ADP to ATP.

Figure 3
Leaf spots and chlorosis caused by the
Alternaria alternata toxin


2.  Cercosporin: Cercosporin is produced by the fungus Cercospora and by several other fungi. It causes damaging leaf spot and blight diseases of many crop plants, such as Cercospora leaf spot of zinnia (Fig. 4A) and gray leaf spot of corn (Fig. 4B). Cercosporin is unique among fungal toxins in that it is activated by light and becomes toxic to plants by generating activated species of oxygen, particularly single oxygen. The generated active single oxygen destroys the membranes of host plants and provides nutrients for this intercellular pathogen.

Figure 4
Leaf spots on zinnia (A) and gray leaf spots on corn (B) caused by the photosensitizing toxin cercosporin, produced by the fungus
Cercospora.


3.Victorin (HV-toxin), is produced by the fungus Cochliobolus (Helminthosporium) victoriae. This fungus appeared in 1945 after the introduction and widespread use of the oat variety Victoria and its derivatives, all of which contained the gene Vb for resistance to crown rust disease. C. victoriae infects the basal portions of susceptible oat plants and produces a toxin that is carried to the leaves, causes a leaf blight, and destroys the entire plant. All other oats and other plant species tested were either immune to the fungus and to the toxin or their sensitivity to the toxin was proportional to their susceptibility to the fungus. Toxin production in the fungus is controlled by a single gene.


Victorin has been purified and its chemical structure has been determined to be a complex chlorinated, partially cyclic pentapeptide. The primary target of the toxin seems to be the cell plasma membrane where victorin seems to bind to several proteins. The possible site of action of victorin seems to be the glycine decar-boxylate complex, which is a key component of the photorespiratory cycle. Considerable evidence, however, indicates that victorin functions as an elicitor that induces components of a resistance response that include many of the features of hypersensitive response and lead to programmed cell death.


4. Fusaric acid: Fusaric acid is a picolinic acid derivative. It is typically isolated from various Fusarium species, and has been proposed for a various therapeutic applications. However, it is primarily used as a research tool. Its mechanism of action is not well understood. It likely inhibits Dopamine beta-hydroxylase (the enzyme that converts dopamine to norepinephrine). It may also have other actions, such as the inhibition of cell proliferation and DNA synthesis.

Figure 5
Chemical structure of fusaric acid

Pathotoxin

Pathotoxin is a chemical of biological origin, other than an enzyme, that plays an important role in a plant disease. Most pathotoxins are produced by plant pathogenic fungi or bacteria, but some are produced by higher plants, and one has been reported to be the product of an interaction between a plant and a bacterial pathogen. Some pathogen-produced pathotoxins are highly selective in that they cause severe damage and typical disease symptoms only on plants susceptible to the pathogens that produce them. Others are nonselective and are equally toxic to plants susceptible or resistant to the pathogen involved. A few pathotoxins are species-selective, and are damaging to many but not all plant species. In these instances, some plants resistant to the pathogen are sensitive to its toxic product.

Aflatoxins

Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, the most notable ones being Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are toxic and among the most carcinogenic substances known. After entering the body, aflatoxins may be metabolized by the liver to a reactive epoxide intermediate or hydroxylated to become the less harmful aflatoxin M1.

Harmful effect of aflatoxins


High-level aflatoxin exposure produces an acute hepatic necrosis, resulting later in cirrhosis, and/or carcinoma of the liver. Acute hepatic failure is made manifest by hemorrhage, edema, alteration in digestion, changes to the absorption and/or metabolism of nutrients, and mental changes and/or coma.

Aflatoxins detection in human

There are two principal techniques that have been used to detect levels of aflatoxin in humans:

1.Measuring the AFB1-guanine adduct in the urine of subjects. The presence of this breakdown product indicates exposure to aflatoxin B1 in the past 24 hours. However, this technique measures only recent exposure, and, due to the half-life of this metabolite, the level of AFB1-guanine measured can vary from day to day, based on diet, and thus is not ideal for assessing long-term exposure.

2.Measurement of the AFB1-albumin adduct level in the blood serum. This approach provides a more integrated measure of exposure over several weeks/months.

Major types of aflatoxins

At least 14 different types of aflatoxin are produced in nature. Aflatoxin B1 is considered the most toxic and is produced by both Aspergillus flavus and Aspergillus parasiticus. Aflatoxin G1 and G2 are produced exclusively by A. parasiticus. While the presence of Aspergillus in food products does not always indicate harmful levels of aflatoxin are also present, it does imply a significant risk in consumption. Aflatoxins M1, M2 were originally discovered in the milk of cows that fed on moldy grain. These compounds are products of a conversion process in the animal's liver. However, aflatoxin M1 is present in the fermentation broth of Aspergillus parasiticus.



1.Aflatoxin B1 & B2 : produced by Aspergillus flavus and A. parasiticus.

2.Aflatoxin G1 & G2 : produced by Aspergillus parasiticus.

3.Aflatoxin M1 : metabolite of aflatoxin B1 in humans and animals (can come from a mother's milk).

4.Aflatoxin M2 : metabolite of aflatoxin B2 in milk of cattle fed on contaminated foods.

5.Aflatoxicol.

Figure 6
Chemical structure of aflatoxin B1

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