Xenobiotic

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A xenobiotic is a chemical substance found within an organism that is not naturally produced or expected to be present within the organism. It can also cover substances that are present in much higher concentrations than are usual. Natural compounds can also become xenobiotics if they are taken up by another organism, such as the uptake of natural human hormones by fish found downstream of sewage treatment plant outfalls, or the chemical defenses produced by some organisms as protection against predators. [1] The term "xenobiotic" is also used to refer to organs transplanted from one species to another.

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The term "xenobiotics", however, is very often used in the context of pollutants such as dioxins and polychlorinated biphenyls and their effect on the biota, because xenobiotics are understood as substances foreign to an entire biological system, i.e. artificial substances, which did not exist in nature before their synthesis by humans. The term xenobiotic is derived from the Greek words ξένος (xenos) = foreigner, stranger and βίος (bios) = life, plus the Greek suffix for adjectives -τικός, -ή, -όν (-tikos, -ē, -on). Xenobiotics may be grouped as carcinogens, drugs, environmental pollutants, food additives, hydrocarbons, and pesticides.

Xenobiotic metabolism

The body removes xenobiotics by xenobiotic metabolism. This consists of the deactivation and the excretion of xenobiotics and happens mostly in the liver. Excretion routes are urine, feces, breath, and sweat. Hepatic enzymes are responsible for the metabolism of xenobiotics by first activating them (oxidation, reduction, hydrolysis, and/or hydration of the xenobiotic), and then conjugating the active secondary metabolite with glucuronic acid, sulfuric acid, or glutathione, followed by excretion in bile or urine. An example of a group of enzymes involved in xenobiotic metabolism is hepatic microsomal cytochrome P450. These enzymes that metabolize xenobiotics are very important for the pharmaceutical industry because they are responsible for the breakdown of medications. A species with this unique cytochrome P450 system is Drosophila mettleri, which uses xenobiotic resistance to exploit a wider nesting range including both soil moistened with necrotic exudates and necrotic plots themselves.

Although the body is able to remove xenobiotics by reducing it to a less toxic form through xenobiotic metabolism then excreting it, it is also possible for it to be converted into a more toxic form in some cases. This process is referred to as bioactivation and can result in structural and functional changes to the microbiota. [2] Exposure to xenobiotics can disrupt the microbiome community structure, either by increasing or decreasing the size of certain bacterial populations depending on the substance. Functional changes that result vary depending on the substance and can include increased expression in genes involved in stress response and antibiotic resistance, changes in the levels of metabolites produced, etc. [3]

Organisms can also evolve to tolerate xenobiotics. An example is the co-evolution of the production of tetrodotoxin in the rough-skinned newt and the evolution of tetrodotoxin resistance in its predator, the Common Garter Snake. In this predator–prey pair, an evolutionary arms race has produced high levels of toxin in the newt and correspondingly high levels of resistance in the snake. [4] This evolutionary response is based on the snake evolving modified forms of the ion channels that the toxin acts upon, so becoming resistant to its effects. [5] Another example of a xenobiotic tolerance mechanism is the use of ATP-binding cassette (ABC) transporters, which is largely exhibited in insects. [6] Such transporters contribute to resistance by enabling the transport of toxins across the cell membrane, thus preventing accumulation of these substances within cells.

Xenobiotics in the environment

Xenobiotic substances are an issue for sewage treatment systems, since they are many in number, and each will present its own problems as to how to remove them (and whether it is worth trying to)

Some xenobiotics substances are resistant to degradation. Xenobiotics such as polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and trichloroethylene (TCE) accumulate in the environment due to their recalcitrant properties and have become an environmental concern due to their toxicity and accumulation. This occurs particularly in the subsurface environment and water sources, as well as in biological systems, having the potential to impact human health. [7] Some of the main sources of pollution and the introduction of xenobiotics into the environment come from large industries such as pharmaceuticals, fossil fuels, pulp and paper bleaching and agriculture. [8] For example, they may be synthetic organochlorides such as plastics and pesticides, or naturally occurring organic chemicals such as polyaromatic hydrocarbons (PAHs) and some fractions of crude oil and coal.

Microorganisms may be a viable solution to this issue of environmental pollution by the degradation of the xenobiotics; a process known as bioremediation. [9] Microorganisms are able to adapt to xenobiotics introduced into the environment through horizontal gene transfer, in order to make use of such compounds as energy sources. [8] This process can be further altered to manipulate the metabolic pathways of microorganisms in order to degrade harmful xenobiotics under specific environmental conditions at a more desirable rate. [8] Mechanisms of bioremediation include both genetically engineering microorganisms and isolating the naturally occurring xenobiotic degrading microbes. [9] Research has been conducted to identify the genes responsible for the ability of microorganisms to metabolize certain xenobiotics and it has been suggested that this research can be used in order to engineer microorganisms specifically for this purpose. [9] Not only can current pathways be engineered to be expressed in other organisms, but the creation of novel pathways is a possible approach. [8]

Xenobiotics may be limited in the environment and difficult to access in areas such as the subsurface environment. [8] Degradative organisms can be engineered to increase mobility in order to access these compounds, including enhanced chemotaxis. [8] One limitation of the bioremediation process is that optimal conditions are required for proper metabolic functioning of certain microorganisms, which may be difficult to meet in an environmental setting. [7] In some cases a single microorganism may not be capable of performing all metabolic processes required for degradation of a xenobiotic compound and so "syntrophic bacterial consortia" may be employed. [8] In this case, a group of bacteria work in conjunction, resulting in dead end products from one organism being further degraded by another organism. [7] In other cases, the products of one microorganisms may inhibit the activity another, and thus a balance must be maintained. [8]

Many xenobiotics produce a variety of biological effects, which is used when they are characterized using bioassay. Before they can be registered for sale in most countries, xenobiotic pesticides must undergo extensive evaluation for risk factors, such as toxicity to humans, ecotoxicity, or persistence in the environment. For example, during the registration process, the herbicide, cloransulam-methyl was found to degrade relatively quickly in soil. [10]

Inter-species organ transplantation

The term xenobiotic is also used to refer to organs transplanted from one species to another. For example, some researchers hope that hearts and other organs could be transplanted from pigs to humans. Many people die every year whose lives could have been saved if a critical organ had been available for transplant. Kidneys are currently the most commonly transplanted organ. Xenobiotic organs would need to be developed in such a way that they would not be rejected by the immune system.

See also

Drug metabolism – Xenobiotic metabolism is redirected to the special case: Drug metabolism.

Related Research Articles

Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance faster than it can be lost or eliminated by catabolism and excretion. Thus, the longer the biological half-life of a toxic substance, the greater the risk of chronic poisoning, even if environmental levels of the toxin are not very high. Bioaccumulation, for example in fish, can be predicted by models. Hypothesis for molecular size cutoff criteria for use as bioaccumulation potential indicators are not supported by data. Biotransformation can strongly modify bioaccumulation of chemicals in an organism.

<span class="mw-page-title-main">Excretion</span> Elimination by an organism of metabolic waste products

Excretion is a process in which metabolic waste is eliminated from an organism. In vertebrates, this is primarily carried out by the lungs, kidneys, and skin. This is in contrast with secretion, where the substance may have specific tasks after leaving the cell. Excretion is an essential process in all forms of life. For example, in placental mammals, urine is expelled through the urethra, which is part of the excretory system. In unicellular organisms, waste products are discharged directly through the surface of the cell.

Detoxification or detoxication is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of drug withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. In medicine, detoxification can be achieved by decontamination of poison ingestion and the use of antidotes as well as techniques such as dialysis and chelation therapy.

<span class="mw-page-title-main">Bioremediation</span> Process used to treat contaminated media such as water and soil

Bioremediation broadly refers to any process wherein a biological system, living or dead, is employed for removing environmental pollutants from air, water, soil, flue gasses, industrial effluents etc., in natural or artificial settings. The natural ability of organisms to adsorb, accumulate, and degrade common and emerging pollutants has attracted the use of biological resources in treatment of contaminated environment. In comparison to conventional physicochemical treatment methods bioremediation may offer advantages as it aims to be sustainable, eco-friendly, cheap, and scalable.

<span class="mw-page-title-main">Phytoremediation</span> Decontamination technique using living plants

Phytoremediation technologies use living plants to clean up soil, air and water contaminated with hazardous contaminants. It is defined as "the use of green plants and the associated microorganisms, along with proper soil amendments and agronomic techniques to either contain, remove or render toxic environmental contaminants harmless". The term is an amalgam of the Greek phyto (plant) and Latin remedium. Although attractive for its cost, phytoremediation has not been demonstrated to redress any significant environmental challenge to the extent that contaminated space has been reclaimed.

Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems. More generally, xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as any drug or poison. These pathways are a form of biotransformation present in all major groups of organisms and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds. The study of drug metabolism is called pharmacokinetics.

Biological augmentation is the addition of archaea or bacterial cultures required to speed up the rate of degradation of a contaminant. Organisms that originate from contaminated areas may already be able to break down waste, but perhaps inefficiently and slowly.

<span class="mw-page-title-main">Mycoremediation</span> Process of using fungi to degrade or sequester contaminants in the environment

Mycoremediation is a form of bioremediation in which fungi-based remediation methods are used to decontaminate the environment. Fungi have been proven to be a cheap, effective and environmentally sound way for removing a wide array of contaminants from damaged environments or wastewater. These contaminants include heavy metals, organic pollutants, textile dyes, leather tanning chemicals and wastewater, petroleum fuels, polycyclic aromatic hydrocarbons, pharmaceuticals and personal care products, pesticides and herbicides in land, fresh water, and marine environments.

Cometabolism is defined as the simultaneous degradation of two compounds, in which the degradation of the second compound depends on the presence of the first compound. This is in contrast to simultaneous catabolism, where each substrate is catabolized concomitantly by different enzymes. Cometabolism occurs when an enzyme produced by an organism to catalyze the degradation of its growth-substrate to derive energy and carbon from it is also capable of degrading additional compounds. The fortuitous degradation of these additional compounds does not support the growth of the bacteria, and some of these compounds can even be toxic in certain concentrations to the bacteria.

Organohalide respiration (OHR) (previously named halorespiration or dehalorespiration) is the use of halogenated compounds as terminal electron acceptors in anaerobic respiration. Organohalide respiration can play a part in microbial biodegradation. The most common substrates are chlorinated aliphatics (PCE, TCE, chloroform) and chlorinated phenols. Organohalide-respiring bacteria are highly diverse. This trait is found in some Campylobacterota, Thermodesulfobacteriota, Chloroflexota (green nonsulfur bacteria), low G+C gram positive Clostridia, and ultramicrobacteria.

Microbial biodegradation is the use of bioremediation and biotransformation methods to harness the naturally occurring ability of microbial xenobiotic metabolism to degrade, transform or accumulate environmental pollutants, including hydrocarbons, polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs), heterocyclic compounds, pharmaceutical substances, radionuclides and metals.

<span class="mw-page-title-main">Xenobiotic metabolism</span>

Xenobiotic metabolism is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons. These pathways are a form of biotransformation present in all major groups of organisms, and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds; however, in cases such as in the metabolism of alcohol, the intermediates in xenobiotic metabolism can themselves be the cause of toxic effects.

<span class="mw-page-title-main">Phototrophic biofilm</span> Microbial communities including microorganisms which use light as their energy source

Phototrophic biofilms are microbial communities generally comprising both phototrophic microorganisms, which use light as their energy source, and chemoheterotrophs. Thick laminated multilayered phototrophic biofilms are usually referred to as microbial mats or phototrophic mats. These organisms, which can be prokaryotic or eukaryotic organisms like bacteria, cyanobacteria, fungi, and microalgae, make up diverse microbial communities that are affixed in a mucous matrix, or film. These biofilms occur on contact surfaces in a range of terrestrial and aquatic environments. The formation of biofilms is a complex process and is dependent upon the availability of light as well as the relationships between the microorganisms. Biofilms serve a variety of roles in aquatic, terrestrial, and extreme environments; these roles include functions which are both beneficial and detrimental to the environment. In addition to these natural roles, phototrophic biofilms have also been adapted for applications such as crop production and protection, bioremediation, and wastewater treatment.

In aquatic toxicology, bioconcentration is the accumulation of a water-borne chemical substance in an organism exposed to the water.

Bioremediation of petroleum contaminated environments is a process in which the biological pathways within microorganisms or plants are used to degrade or sequester toxic hydrocarbons, heavy metals, and other volatile organic compounds found within fossil fuels. Oil spills happen frequently at varying degrees along with all aspects of the petroleum supply chain, presenting a complex array of issues for both environmental and public health. While traditional cleanup methods such as chemical or manual containment and removal often result in rapid results, bioremediation is less labor-intensive, expensive, and averts chemical or mechanical damage. The efficiency and effectiveness of bioremediation efforts are based on maintaining ideal conditions, such as pH, RED-OX potential, temperature, moisture, oxygen abundance, nutrient availability, soil composition, and pollutant structure, for the desired organism or biological pathway to facilitate reactions. Three main types of bioremediation used for petroleum spills include microbial remediation, phytoremediation, and mycoremediation. Bioremediation has been implemented in various notable oil spills including the 1989 Exxon Valdez incident where the application of fertilizer on affected shoreline increased rates of biodegradation.

Polychorinated biphenyls, or PCBs, are a type of chemical that was widely used in the 1960s and 1970s, and which are a contamination source of soil and water. They are fairly stable and therefore persistent in the environment. Bioremediation of PCBs is the use of microorganisms to degrade PCBs from contaminated sites, relying on multiple microorganisms' co-metabolism. Anaerobic microorganisms dechlorinate PCBs first, and other microorganisms that are capable of doing BH pathway can break down the dechlorinated PCBs to usable intermediates like acyl-CoA or carbon dioxide. If no BH pathway-capable microorganisms are present, dechlorinated PCBs can be mineralized with help of fungi and plants. However, there are multiple limiting factors for this co-metabolism.

<i>In situ</i> bioremediation

Bioremediation is the process of decontaminating polluted sites through the usage of either endogenous or external microorganism. In situ is a term utilized within a variety of fields meaning "on site" and refers to the location of an event. Within the context of bioremediation, in situ indicates that the location of the bioremediation has occurred at the site of contamination without the translocation of the polluted materials. Bioremediation is used to neutralize pollutants including Hydrocarbons, chlorinated compounds, nitrates, toxic metals and other pollutants through a variety of chemical mechanisms. Microorganism used in the process of bioremediation can either be implanted or cultivated within the site through the application of fertilizers and other nutrients. Common polluted sites targeted by bioremediation are groundwater/aquifers and polluted soils. Aquatic ecosystems affected by oil spills have also shown improvement through the application of bioremediation. The most notable cases being the Deepwater Horizon oil spill in 2010 and the Exxon Valdez oil spill in 1989. Two variations of bioremediation exist defined by the location where the process occurs. Ex situ bioremediation occurs at a location separate from the contaminated site and involves the translocation of the contaminated material. In situ occurs within the site of contamination In situ bioremediation can further be categorized by the metabolism occurring, aerobic and anaerobic, and by the level of human involvement.

<span class="mw-page-title-main">Pharmacomicrobiomics</span>

Pharmacomicrobiomics, proposed by Prof. Marco Candela for the ERC-2009-StG project call, and publicly coined for the first time in 2010 by Rizkallah et al., is defined as the effect of microbiome variations on drug disposition, action, and toxicity. Pharmacomicrobiomics is concerned with the interaction between xenobiotics, or foreign compounds, and the gut microbiome. It is estimated that over 100 trillion prokaryotes representing more than 1000 species reside in the gut. Within the gut, microbes help modulate developmental, immunological and nutrition host functions. The aggregate genome of microbes extends the metabolic capabilities of humans, allowing them to capture nutrients from diverse sources. Namely, through the secretion of enzymes that assist in the metabolism of chemicals foreign to the body, modification of liver and intestinal enzymes, and modulation of the expression of human metabolic genes, microbes can significantly impact the ingestion of xenobiotics.

<span class="mw-page-title-main">Synthetic microbial consortia</span>

Synthetic microbial consortia or Synthetic microbial communities are multi-population systems that can contain a diverse range of microbial species, and are adjustable to serve a variety of industrial, ecological, and tautological interests. For synthetic biology, consortia take the ability to engineer novel cell behaviors to a population level.

Hydrocarbonoclastic bacteria are a heterogeneous group of prokaryotes which can degrade and utilize hydrocarbon compounds as source of carbon and energy. Despite being present in most of environments around the world, several of these specialized bacteria live in the sea and have been isolated from polluted seawater.

References

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  2. ↑ Park, B.K.; Laverty, H.; Srivastava, A.; Antoine, D.J.; Naisbitt, D.; Williams, D.P. (2011). "Drug bioactivation and protein adduct formation in the pathogenesis of drug-induced toxicity". Chemico-Biological Interactions. 192 (1–2): 30–36. doi:10.1016/j.cbi.2010.09.011. PMID   20846520.
  3. ↑ Lu, Kun; Mahbub, Ridwan; Fox, James G. (31 August 2015). "Xenobiotics: Interaction with the Intestinal Microflora". ILAR Journal. 56 (2): 218–227. doi:10.1093/ilar/ilv018. ISSN   1084-2020. PMC   4654756 . PMID   26323631.
  4. ↑ Brodie ED, Ridenhour BJ, Brodie ED (2002). "The evolutionary response of predators to dangerous prey: hotspots and coldspots in the geographic mosaic of coevolution between garter snakes and newts". Evolution. 56 (10): 2067–82. doi:10.1554/0014-3820(2002)056[2067:teropt]2.0.co;2. PMID   12449493.
  5. ↑ Geffeney S, Brodie ED, Ruben PC, Brodie ED (2002). "Mechanisms of adaptation in a predator–prey arms race: TTX-resistant sodium channels". Science. 297 (5585): 1336–9. Bibcode:2002Sci...297.1336G. doi:10.1126/science.1074310. PMID   12193784. S2CID   8816337.
  6. ↑ Broehan, Gunnar; Kroeger, Tobias; Lorenzen, Marcé; Merzendorfer, Hans (16 January 2013). "Functional analysis of the ATP-binding cassette (ABC) transporter gene family of Tribolium castaneum". BMC Genomics. 14: 6. doi: 10.1186/1471-2164-14-6 . ISSN   1471-2164. PMC   3560195 . PMID   23324493.
  7. 1 2 3 Singh, Ajay; Ward, Owen P., eds. (2004). Biodegradation and bioremediation. Berlin: Springer. ISBN   978-3540211013. OCLC   54529445.
  8. 1 2 3 4 5 6 7 8 Díaz, Eduardo (September 2004). "Bacterial degradation of aromatic pollutants: a paradigm of metabolic versatility". International Microbiology. 7 (3): 173–180. ISSN   1139-6709. PMID   15492931.
  9. 1 2 3 Singleton, Ian (January 1994). "Microbial metabolism of xenobiotics: Fundamental and applied research". Journal of Chemical Technology and Biotechnology. 59 (1): 9–23. doi:10.1002/jctb.280590104.
  10. ↑ Wolt JD, Smith JK, Sims JK, Duebelbeis DO (1996). "Products and kinetics of cloransulam-methyl aerobic soil metabolism". J. Agric. Food Chem. 44: 324–332. doi:10.1021/jf9503570.
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